Search

Background Catheter-associated urinary tract infections (CAUTI) are among the most frequent healthcare-associated infections in the world. They are associated with increased mortality, prolonged hospital stay and increased healthcare costs. The objective of this study was to evaluate the efficacy of the noble metal alloy (NMA) coated BIP Foley Catheter in preventing the incidence of symptomatic CAUTI in a large cohort of patients in India. Methods This multi-center, prospective study included 1000 adult patients admitted to six hospitals across India for urology, surgery and ICU requiring urethral catheterization and admission for ≥ 48 h. Patients were allocated to the NMA-coated BIP Foley Catheter group or a non-coated control catheter group, with a randomization ratio of 3:1. CAUTI surveillance was conducted at study entry, upon catheter removal, and 2 days after catheter removal. For statistical analysis, categorical data (e.g. gender) were compared using the chi-square or Fischer test, and numerical data were compared using the two-sample t-test. Associations were evaluated using logistic regression. Results and conclusions The incidence of symptomatic CAUTI was reduced by 69% in the BIP Foley Catheter group compared to the control group (6.5 vs 20.8 CAUTI/1000 catheter days), with an incidence rate ratio of 0.31 (95% confidence interval: 0.21–0.46; p p = 0.001). In conclusion, the NMA-coated BIP Foley Catheter was effective in reducing CAUTI and was well tolerated, with a lower incidence of adverse events compared to the uncoated catheter. Trial registration This study was registered prospectively (28 September 2015) in the Clinical Trials Registry of India (trial number CTRI/2015/09/006220; http://ctri.nic.in/Clinicaltrials/showallp.php?mid1=12631&EncHid=&userName=bactiguard).

Background To ascertain the validity of kidney paired donations (KPDs) as an alternative strategy for increasing living donor kidney transplantations (LDKTs) in an LDKT-dominated transplant programme since directed kidney transplantation, ABO-incompatible or crossmatch-positive pairs are not feasible due to costs and infectious complications. Methods This was a prospective single-centre study of 77 KPD transplantations (25 two-way, 7 three-way and 1 six-way exchange) from 1 January 2015 to 1 January 2016 of 158 registered donor recipient pairs. During this period, a total of 380 kidney transplantations [71 deceased donor kidney transplantations (DDKTs), 309 LDKTs] were performed. The reasons for opting for KPD were ABO incompatibility (n = 45), sensitization (n = 26) and better matching (n = 6). Results KPD matching was facilitated in 62% (n = 98) of transplants. In all, 48.7% (n = 77) of the transplants were completed in 2015, whereas 13.3% (n = 21) of the matched patients were to undergo transplant surgery in early 2016 after getting legal permission. The waiting time for KPD was shorter compared with DDKT. The death-censored graft survival and patient survival were 98.7% (n = 76) and 93.5% (n = 72), respectively. In all, 14.2% (n = 11) of patients had acute rejection. Match rates among sensitized (n = 60) and O group patients (n = 62) were 58.3% (n = 35) and 41.9% (n = 26), respectively. Of these, 43.3% (n = 26) and 29% (n = 18) of transplants were completed and 15% (n = 9) and 12.9% (n = 8), respectively, are waiting for legal permission. Conclusions LDKT increased by 25% in 1 year in our single-centre KPD programme. Our key to success was the formation of a KPD registry, awareness and active counselling programs and developing a dedicated team.

One third of healthy willing living kidney donors are rejected due to ABO blood group incompatibility and donor specific antibody. This increases pre-transplant dialysis duration leading to increased morbidity and mortality on the kidney transplantation waiting list. Over the last decade kidney paired donation is most rapidly increased source of living kidney donors. In a kidney transplantation program dominated by living donor kidney transplantation, kidney paired donation is a legal and valid alternative strategy to increase living donor kidney transplantation. This is more useful in countries with limited resources where ABO incompatible kidney transplantation or desensitization protocol is not feasible because of costs/infectious complications and deceased donor kidney transplantation is in initial stages. The matching allocation, ABO blood type imbalance, reciprocity, simultaneity, geography were the limitation for the expansion of kidney paired donation. Here we describe different successful ways to increase living donor kidney transplantation through kidney paired donation. Compatible pairs, domino chain, combination of kidney paired donation with desensitization or ABO incompatible transplantation, international kidney paired donation, non-simultaneous, extended, altruistic donor chain and list exchange are different ways to expand the donor pool. In absence of national kidney paired donation program, a dedicated kidney paired donation team will increase access to living donor kidney transplantation in individual centres with team work. Use of social networking sites to expand donor pool, HLA based national kidney paired donation program will increase quality and quantity of kidney paired donation transplantation. Transplant centres should remove the barriers to a broader implementation of multicentre, national kidney paired donation program to further optimize potential of kidney paired donation to increase transplantation of O group and sensitized patients. This review assists in the development of similar programs in other developing countries.

Background: Timely diagnosis of invasive fungal infections (IFI) in renal transplant (RT) patients on immunosuppression is often difficult, jeopardizing their life and graft. We reported IFI and their causative fungal agents in post-RT patients. Materials and methods: This was a retrospective 6-year clinical study carried out from 2010 to 2015 on 1900 RT patients. Clinical data included patient-donor demographics, time to onset of infection, risk factors and graft function in terms of serum creatinine (SCr). To identify IFI, we examined bronchoalveolar lavage (BAL), blood, tissue, and wound swab samples by conventional mycological methods. Results: IFI were diagnosed in 30 (1.56%) patients on triple immunosuppression, mainly males (n = 25) with mean age of 36.57 ± 11.9 years at 13.12 ± 18.35 months post-RT. Aspergillus species was identified in 11 BAL, one tissue, and one wound specimen each, 30.76% of these were fatal and 15.38% caused graft loss; Candida albicans was in nine BAL, four blood, two wound swab, and one tissue specimens, 25% of these were fatal and 25% had graft loss and one mucor in BAL which was fatal. Seven patients were diabetic, 10 had superadded cytomegalovirus infection, and 15 were anti-rejected. Conclusion: IFI are associated with increased morbidity and mortality in RT patients. Triple immunosuppression, broad spectrum antibiotics for ≥ two weeks, diabetes and superadded infection are added risks for these patients. Prevention, early diagnosis, and appropriate management are necessary to improve their prognosis.

The best and most cost-effective treatment for end-stage renal disease patients is living donor (LD) renal transplantation. It has survival benefit compared to deceased donor (DD) kidney transplant (DDKT) and long-term dialysis and provides a better quality of life. Efficient and effective kidney allocation methods are increasingly necessary to address the problem of organ scarcity. The use of kidney paired donation transplant has increased access to LD kidney transplantation (LDKT) with outstanding results. ABO-incompatible kidney transplantation (KT) and desensitization protocol can expand the donor pool, but as integral to any aggressive immunosuppression protocol, they are associated with increased risk of infection and malignancy. Given the widespread organ shortage, DDKT from donors with sepsis, donors who died from snakebite or acute kidney injury, controlled donation after cardiac death, older donors, can be considered for KT with an acceptable outcome. The acceptable outcome can be achieved with dual KT using kidneys from expanded criteria donors in older population. Dual KT from pediatric donors to adult recipients or from adult marginal DDs is a promising way to expand the donor pool. Carefully selected donor with HIV, HCV, and HBV positivity is not a contraindication for living kidney donation. Careful and meticulous selection of patient and donor is essential for successful outcome. Affordable or free transplantation is other way to increase transplantation rate in developing country. The community support can make transplantation available free to the poor patients under community-government partnership. Various steps should be taken to promote LDKT and DDKT program.

AIM To avoid desensitization protocols and ABO incompatible kidney transplantation (KT) due to high costs and increased risk of infections from intense immunosuppression. METHODS We present institutional ethical review board - approved study of single center 6-way kidney exchange transplantation. The participants comprised ABO incompatibility (n = 1); positive cross-match and/or presence of donor specific antibody (n = 5). The average time required from registration in kidney paired donation (KPD) registry to find suitable donors was 45 d and time required to perform transplants after legal permission was 2 mo. RESULTS Graft and patient survival were 100%, and 100%, respectively. One patient had biopsy-proven acute borderline T cell rejection (Banff update 2013, type 3). Mean serum creatinine was 0.8 mg/dL at 9 mo follow-up. The waiting time in KPD was short as compared to deceased donor KT. CONCLUSION We report first non-simultaneous, single center, 6-way kidney exchange transplantation from India. Our experience will encourage other centers in India to undertake this practice.

Fungal infection represents 5% of the infections of post renal transplant recipients. The frequency of invasive Aspergillus ranges from 0.5% to 2.2% with a mortality rate of 88%. In renal transplantation, Aspergillus infection usually affects primarily the lungs with occasional dissemination and the central nervous system. Involvement of a renal allograft in the isolated form is rare. A-35-year-old male post-renal transplant patient presented in our institute for routine follow up examination. Ultrasound and computed tomography (CT) were conducted in our radiology department, suggestive of abscess formation in mid pole of transplanted kidney. The patient did not have any clinical symptoms. His serum creatinine level was also within normal limit. Diagnosis of Aspergillus fumigates was made by aspiration of pus. Treatment started according to culture and sensitivity report. Ultimately graft nephrectomy was performed to control infection. Aspergillus infection of a renal allograft remains a key issue for nephrologists and infection specialists. For diagnosis of fungal infection, a high index of suspicious is necessary. In the present case, the infected allograft nephrectomy and the elimination of immune-compromised state and the prompt administration of antifungal therapy, made recovery possible. However, early diagnosis remains difficult.

BACKGROUND Globally there is an increase in incidence of chronic kidney diseases (CKDs). Diabetes mellitus (DM), hypertension and stone diseases are the major risk factors for CKD. We organized kidney disease screening camps in a semi-urban population of Gujarat, India on the occasion of World Kidney Day (WKD). METHODS Voluntary participants from six towns were screened. Estimated glomerular filtration rate (eGFR) was calculated by the Modification of Diet in Renal Disease formula and CKD was defined as an eGFR

Clinical and biochemical manifestations of lecithin-cholesterol acyltransferase (LCAT) deficiency include an abnormal lipid profile (characterized by hypercholesterolemia with markedly decreased high-density lipoprotein cholesterol [HDL-C] and hypertriglyceridemia), corneal opacities, hematologic abnormalities (normochromic anemia of varying intensity), splenomegaly, variable early coronary artery disease and nephropathy (initially proteinuria followed by progressive deterioration of renal function). We presented a patient with nephrotic syndrome, which renal biopsy revealed classic features of LCAT deficiency. To our knowledge, the present case is the first reported case of LCAT deficiency presenting with symptoms related to nephrotic syndrome in a patient with no obvious family history without any corneal deposits and normal HDL-C levels.

Mauriac syndrome is an uncommon complication of poorly-controlled type 1 diabetes mellitus (T1DM) reported in children 13–17 years of age. It manifests as delayed growth, hepatomegaly, elevated liver enzymes and serum lipids, and glycogen accumulation in hepatocytes. Common presenting features include short stature, growth retardation, moon facies, protuberant abdomen and proximal muscle wasting. Since the advent of long- and intermediate-acting insulin, this syndrome is now rarely encountered. We report the case of a 16-year-old male who had a 13-year history of T1DM and was diagnosed with Mauriac syndrome. He was treated with biphasic isophane insulin and recovered – good glycaemic control was maintained, his height increased from 128cm to 141.5cm, hepatomegaly disappeared with normal liver enzymes, and the onset of pubertal spurt at eight months' follow up was shown. In conclusion, ensuring compliance with insulin therapy, and providing supportive treatment, nutritional support and good follow-up care can help to mitigate most of the complications relating to Mauriac syndrome. Copyright © 2017 John Wiley & Sons.

Aim: Complex vascular anatomy poses a major challenge to the donor surgeon. Here, we have described the technical nuances in retroperitoneoscopic living donor nephrectomy for the left kidney in the situations of a rare vascular anomaly of duplication of inferior vena. Materials and Methods: Between September 2005 and June 2016, 1460 retroperitoneoscopic living donor nephrectomy were carried out in single surgical unit of our institution. Out of these four donors were found to have duplication of inferior vena cava (IVC). We retrospectively analyzed the prospectively collected data of these donors and studied the operative details for managing the duplicated limb of the IVC. Results: The mean age of the donors was 42.5 (range 30–54) years. Mean body mass index was 26.9 (range 25.2–28.6) kg/m2. Mean operative time (defined as between giving skin incision to the skin closure [O. T]), was 230 (range 185–310 min). Mean Warm ischemia time (defined from clamping of the renal artery to the starting of the cold HTK perfusion, [WIT]) was 136 s (range 105–178 s). In two cases, the renal vein could be controlled distal to the duplicated limb. In one case, the duplicated limb was clipped while in another a stapler was used to take a cuff of IVC. Conclusion: Retroperitoneoscopic donor nephrectomy can be performed safely in cases of duplication of IVC. Preoperative computerized tomography angiography with vascular reconstruction and surgical expertise is desirable in carrying out the procedure.

The pharmacology of the sirolimus and their use in renal transplant recipients are discussed here. In majority of the transplant centers, sirolimus whole-blood concentrations are measured by enzyme-linked immunoassays and high-performance liquid chromatography (HPLC) with ultraviolet or mass spectrometry detection. HPLC measures the parent drug and is very accurate but time-consuming. The recommended time for collection is 1 h prior to the next oral dose. Because of metabolic interactions, sirolimus should be given 4 h after cyclosporine, whereas sirolimus and Tacrolimus can be given simultaneously. The target sirolimus levels should be 5–15 ng/mL depending on immunologic risk, time of conversion and other immunosuppressive drugs. Sirolimus trough concentrations >15 ng/mL have been correlated with side effects such as hypertriglyceridemia, thrombocytopenia, and leukopenia. The 2009 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guidelines for the care of kidney transplant recipients suggest monitoring sirolimus levels (2C). KDIGO recommend that if sirolimus is used, they should not be started until graft function is established and surgical wounds are healed (1B). KDIGO recommend that the combined use of sirolimus and calcineurin inhibitor (CNI) should be avoided, because they potentiate nephrotoxicity, particularly if used in the early period following transplantation. Conversion from CNI to sirolimus is generally not recommended when proteinuria >800 mg/day, acute rejection during the 3 months before conversion, estimated GFR

To determine the knowledge, attitudes and practices regarding organ donation in western India.Convenience sampling was used to generate a sample of 250; 200 interviews were successfully completed and used for analysis. Data collection was carried out via face to face interviews based on a pre-tested questionnaire in selected public areas of Ahmedabad, Gujarat state of India. Data entry was made in excel software in codes and analysis was done by SPSS software.About 86% of participants were aware of the term organ donation but knowledge about its various aspects was low. About 48% aware people heard about organ donation through medical fraternity, whereas only about 21% became aware through mass media. About 59% of aware people believed there is a potential danger of donated organs being misused, abused or misappropriated. About 47% of aware people said they would consider donating organs, while only 16% said they would definitely donate irrespective of circumstances. Around 97.67% participants said they would prefer to donate to nonsmokers. About 74.41% participants were unaware about any legislation regarding organ donation. About 77% participants showed their will to donate to mentally sound persons, and 42.04% participants showed their will to donate even physically challenged people. Around 78 participants felt that they would donate organs to persons irrespective of their religion. About 81% of aware people were of the opinion that consent for organ donation after death should be given by family members. None of the interviewed participants had a donor card.Better knowledge and awareness will help in promoting organ donation. Effective campaign needs to be driven to educate people with relevant information with the involvement of media, doctors and religious scholars.

The prevalence of CKD is increasing worldwide. There is tremendous imbalance in organ supply and demand worldwide. India is having mainly living donor (up to 90%) kidney transplantation program. Majority (up to 45%) of the living donors, although healthy and willing, are rejected due to ABO incompatibility. Deceased donation contributes to

Renal involvement in hepatitis B-polyarteritis nodosa (HBV-PAN) usually occurs in the form of hypertension, microscopic hematuria, proteinuria but nephrotic range proteinuria or renal failure is very uncommon. A 60-year-old man had abdominal pain for 15 days which was followed by bilateral pedal edema in a day and in next three days he had sudden onset bilateral foot drop with numbness. He had weight loss of 10 kg in last 20 days. Pedal edema was pitting, bilateral. Macular skin rashes around both ankles were present. Serum creatinine was 2.4 mg/dl and blood urea nitrogen was 102 mg/dl.24 hour proteinuria was 3.4 g/day. Serum HBsAg, HBeAg and anti-HBc IgM were positive. Serum HBV-DNA level (PCR) was 582917 copies/ml. The nerve conduction study showed axonal and demyelinating polyneuropathy in bilateral lower limbs. A kidney biopsy revealed membranous nephropathy (MN). Doppler for renal vessels was normal. Prednisolone (60 mg/day), plasmapheresis (5 courses) and entecavir (0.5 mg/ every second day) were started. At 2 months follow up, patient improved in the form of grade 3/5 power in both lower limbs with sensory improvement. Twenty-four hours proteinuria decreased to 800 mg/day and serum creatinine reached to 1.5 mg/dl. Polyarteritis nodosa was due to HBV infection, but the etiology of MN was uncertain, as it has rarely been described in PAN. Proteinuria responded to nucleoside analogue therapy. So patient was considered to have an association of classic PAN and MN, both related to HBV. Patient responded to combined treatment of steroid, plasmapheresis and nucleoside analogue.

This study reports our experience of the first 4-way kidney exchange transplant combined with desensitization in India, which allows increased access to living-donor kidney transplant for sensitized patients.Four-way kidney exchange transplant procedures were approved by the ethics committee of our institution and the Organ Transplantation Authorization Committee of state governments of India (as per the Transplantation of Human Organs Act of India). The protocols conformed to Declaration of Istanbul principles and the ethical guidelines of the 1975 Helsinki Declaration. Written informed consent was obtained from patients, donors, and their guardians.In April 2016, our transplant team completed simultaneous 4-way kidney exchange transplant procedures without any medical (rejection and infections) or surgical complications. Reasons for being included for kidney exchange transplant were ABO incom-patible (2 recipients) and sensitization (2 recipients). All 4 recipients had stable graft function with no proteinuria and donor-specific antibody at 11-month follow-up on standard triple immunosup-pression. Patient and graft survival rates were both 100%.To the best of our knowledge, this is the first single-center report of 4-way kidney exchange transplant combined with desensitization from India. This procedure has the potential to expand living-donor kidney transplant in disadvantaged groups (eg, sensitized patients). Recipients who are hard to match due to high panel reactive antibody and difficult to desensitize due to strong donor-specific antibodies can receive a transplant with a combination of kidney exchange and desensitization. Our study suggests that 4-way kidney exchange transplant can be performed in developing countries (India) similar to that shown in programs in developed countries with team work, kidney exchange registry, and counseling.

We present 5-year experience of renal transplantation (RT) with tissue eosinophilia (TE) in renal allograft biopsy (RAB) and its repercussions on the outcome. In total, 1217 recipients underwent RT from 2011 to 2015, and they were evaluated for the presence of ≥4% TE. Group 1 consisted of RT with RAB showing TE, Group 2 consisted of RT with RAB with rejections without TE, and Group 3 consisted of RT without rejections. Group 1 had 27 recipients, Group 2 had 395, and Group 3 had 795 recipients. The outcome in terms of graft function, patient and graft survival were evaluated and compared between three groups. All recipients received standard triple immunosuppression. One-year patient and death-censored graft survival were 80.7% and 82.7% in Group 1, 87.2% and 95.1% in Group 2, and 92.6% and 99.6%, respectively in Group 3 and corresponding mean serum creatinine (SCr, mg/dL) was 1.60 ± 0.45 in Group 1, 1.63 ± 0.58 in Group 2, and 1.19 ± 0.39 Group three, respectively. Five-year patient and death-censored graft survival were 72.9 % and 71.1% for Group 2 and 87% and 98.2% for Group 3 with SCr of 1.63 ± 0.38 and 1.25 ± 0.4, respectively. Group 1 recipients did not appear at five years. At four years posttransplant, patient and death-censored graft survival were 71.7% and 59.5% in Group 1 with SCr of 1.55 ± 0.65 mg/dL. In conclusion, the presence of eosino-phils in a renal allograft is an impending sign of graft damage and eventual graft loss.

Tolerance induction (TI) has been attempted with chimerism/clonal deletion. We report results of TI protocol (TIP) using stem cell therapy (SCT) included adipose derived mesenchymal stem cells (AD-MSC) and hematopoietic stem cells (HSC) in 10 living-donor related renal transplantation (LDRT) patients under non-myeloablative conditioning with Bortezomib, Methylprednisone, rabbit-anti-thymoglobulin and Rituximab, without using conventional immunosuppression. Transplantation was performed following acceptable lymphocyte cross-match, flow cross-match, single antigen assay and negative mixed lymphocyte reaction (MLR). Monitoring included serum creatinine (SCr), donor specific antibodies (DSA) and MLR. Protocol biopsies were planned after 100days and yearly in willing patients. Rescue immunosuppression was planned for rejection/DSA/positive MLR. Over mean 6±0.37year follow-up patient survival was 80% and death-censored graft survival was 90%. Mean SCr was 1.44±0.41mg/dL. This is the first clinical report of sustained TI in LDRT for 6years using SCT.

Background Interleukin-10 secreting B-cells are a major subset of B-regulatory cells (B-regs), commonly recognized as CD19 + /38 hi /24 hi /IL10 + . They carry out immunomodulation by release of specific cytokines and/or cell-to-cell contact. We have generated B-regs in-vitro from donor adipose tissue derived mesenchymal stem cells (AD-MSC) and renal allograft recipient (RAR) peripheral blood mononuclear cells (PBMC) for potential cell therapy. Material and methods Mononuclear cells separated by density gradient centrifugation from 50 ml anti-coagulated blood of 15-RAR and respective donors were analysed for baseline B-regs using appropriate antibodies. Equal amount (20 × 10 6 cells/ml) of stimulator (irradiated at 7.45 Gy/min for 10 min) and responder (non-irradiated) cells were co-cultured with in-vitro generated AD-MSC (1 × 10 6 cells/ml) in proliferation medium containing lipopolysaccharide from E. coli K12 strain at 37 °C with 5% CO 2 . Cells were harvested on day-7 and analyzed for viability, sterility, quantity, morphology and phenotyping. In-vitro generated B-reg levels were compared with baseline B-regs. Results In-vitro generated B-reg count increased to 16.75% from baseline count of 3.35%. Conclusion B-regs can be successfully generated in-vitro from donor AD-MSC and RAR PBMC for potential cell therapy.

In a living donor kidney transplantation (LDKT) dominated transplant programme, kidney paired donation (KPD) may be a cost-effective and valid alternative strategy to increase LDKT in countries with limited resources where deceased donation kidney transplantation (DDKT) is in the initial stages. Here, we report our experience of 300 single-centre KPD transplantations to increase LDKT in India. Between January 2000 and July 2016, 3616 LDKT and 561 DDKT were performed at our transplantation centre, 300 (8.3%) using KPD. The reasons for joining KPD among transplanted patients were ABO incompatibility (n = 222), positive cross-match (n = 59) and better matching (n = 19). A total of 124 two-way (n = 248), 14 three-way (n = 42), one four-way (n = 4) and one six-way exchange (n = 6) yielded 300 KPD transplants. Death-censored graft and patient survival were 96% (n = 288) and 83.3% (n = 250), respectively. The mean serum creatinine was 1.3 mg/dl at a follow-up of 3 ± 3 years. We credit the success of our KPD programme to maintaining a registry of incompatible pairs, counselling on KPD, a high-volume LDKT programme and teamwork. KPD is legal, cost effective and rapidly growing for facilitating LDKT with incompatible donors. This study provides large-scale evidence for the expansion of single-centre LDKT via KPD when national programmes do not exist.

Transplantation tolerance meaning stable graft function without rejection episodes in the absence of immunosuppressive drugs while maintaining third-party immune response intact is still not achieved in clinic. Mesenchymal stem cells (MSCs) are believed to fulfill this dream of tolerance due to their immunomodulatory and tolerogenic properties. This chapter includes introduction on regenerative capacity of the body, immune tolerance, mesenchymal stem cells, their immunomodulatory properties, and how they help in inducing tolerance. The use of MSCs in experimental animal models for treating various diseases and in inducing tolerance has been described briefly, and then the chapter ends with authors’ vision on the future of MSCs and tolerance.

Type-1 diabetes mellitus (T1DM) is a chronic, multifactorial autoimmune disease involving progressive destruction of pancreatic β cells, ultimately resulting in loss of insulin production/secretion, causing hyperglycemia. Replacement of damaged β cells by cell therapy can mitigate this condition and reestablish normal metabolic control. Existing gold standard treatment for T1DM is islet transplantation. However it offers limited rescue from exogenous insulin requirement due to paucity of islets required to reinstate normal blood glucose, immune rejection, and most importantly limited availability of donors. These questions have opened up new horizons for research and management, such as stem cells (SCs), cellular reprogramming, and β-cell regeneration. Results from ongoing clinical trials employing cell therapy designed to arrest T1DM will probably take up the center stage of management of DM in the coming years. SCs are cells with potential to differentiate into many types of cells/progeny and hold promise for providing abundant source of cells for treating T1DM. Surrogate β cells from non-β cells will prove efficient alternative sources, such as adult-/embryonic-/umbilical cord-derived cells. These will have intricate makeup of normal β cells like insulin secretion, which can be utilized in stimulation of β-cell renewal by replication/neogenesis. These cells have revealed increase in endogenous insulin production to some extent alleviating autoimmune demolition of β cells. The present review summarizes the historic as well as current knowledge of T1DM and describes development of cell therapeutics as a promising approach without undesirable side effects.

Background: Strategies for tolerance induction (TI) include induction of chimerism and/or clonal deletion. We present 5-year experience of TI in living-donor related renal transplantation (LDRT) using adipose derived mesenchymal stem cell (AD-MSC) and hematopoietic SC (HSC) infusion with supportive therapy. Methods: Twenty patients divided in 2 equal, demographically balanced groups underwent LDRT under TI protocol (TIP) consisting of conditioning with Bortezomib, Methyl prednisone, rabbit-anti-thymoglobulin and Rituximab. Group-1 were administered in-vitro generated AD-MSC and HSC, group-2 were administered donor specific transfusion. Transplantation was carried out with acceptable lymphocyte cross-match, T and B-cell flow cross-match, single antigen assay and negative mixed lymphocyte reaction (MLR). No conventional immunosuppression was to be administered. Monitoring included serum creatinine (SCr-mg/dL), donor specific antibodies (DSA) and MLR. Protocol biopsies were planned after 100 days and yearly in willing patients. In event of rejection/ DSA/ MLR, rescue immunosuppression was planned. Results: Over mean 5.4 (range: 4.9-6.3) year follow-up patient survival was 80% in group-1 and 90% in group-2; deathcensored graft survival was 90% in group-1 and 70% in group-2. Mean SCr was 1.52 in group-1, and 1.97 in group-2. Five patients from group-1 and 3 from group-2 were on no conventional immunosuppression, 2 patients of group-1 and 1 of group-2 were on two immunosuppressants and 1 patient of group-2 was on 3 immunosuppressants. DSA appeared in 2 patients of group-1 without affecting graft function and 4 of group-2 causing graft dysfunction. MLR was negative in both groups. Conclusion: SCs facilitate TI in LDRT under non-myeloablative conditioning.

According to the Indian chronic kidney disease registry, in 2010 only 2% of end stage kidney disease patients were managed with kidney transplantation, 37% were managed with dialysis and 61% were treated conservatively without renal replacement therapy. In countries like India, where a well-organized deceased donor kidney transplantation program is not available, living donor kidney transplantation is the major source of organs for kidney transplantation. The most common reason to decline a donor for directed living donation is ABO incompatibility, which eliminates up to one third of the potential living donor pool. Because access to transplantation with human leukocyte antigen (HLA)-desensitization protocols and ABO incompatible transplantation is very limited due to high costs and increased risk of infections from more intense immunosuppression, kidney paired donation (KPD) promises hope to a growing number of end stage kidney disease patients. KPD is a rapidly growing and cost-effective living donor kidney transplantation strategy for patients who are incompatible with their healthy, willing living donor. In principle, KPD is feasible for any centre that performs living donor kidney transplantation. In transplant centres with a large living donor kidney transplantation program KPD does not require extra infrastructure, decreases waiting time, avoids transplant tourism and prevents commercial trafficking. Although KPD is still underutilized in India, it has been performed more frequently in recent times. To substantially increase donor pool and transplant rates, transplant centres should work together towards a national KPD program and frame a uniform acceptable allocation policy.

Stem cell therapy is emerging as a viable approach in regenerative medicine. A 31-year-old male with brachial plexus injury had complete sensory-motor loss since 16 years with right pseudo-meningocele at C5-D1 levels and extra-spinal extension up to C7-D1, with avulsion on magnetic resonance imaging and irreversible damage. We generated adipose tissue derived neuronal differentiated mesenchymal stem cells (N-AD-MSC) and bone marrow derived hematopoietic stem cells (HSC-BM). Neuronal stem cells expressed β-3 tubulin and glial fibrillary acid protein which was confirmed on immunofluorescence. On day 14, 2.8 ml stem cell inoculum was infused under local anesthesia in right brachial plexus sheath by brachial block technique under ultrasonography guidance with a 1.5-inch-long 23 gauge needle. Nucleated cell count was 2 × 10 4 /μl, CD34+ was 0.06%, and CD45-/90+ and CD45-/73+ were 41.63% and 20.36%, respectively. No untoward effects were noted. He has sustained recovery with re-innervation over a follow-up of 4 years documented on electromyography-nerve conduction velocity study.

In India, there are a large number of end-stage renal disease (ESRD) patients waiting for renal transplantation (RT). Organ retrieval from brain dead deceased donor (DD) is getting increased attention as the waiting list for organ recipients far exceeds the organ donor pool. In our country, despite a large population, the number of brain dead donors undergoing organ donation is very less. DDRT is the possible solution to bridge the disparity between organ supply and demand. In India, the potential for DDRT is huge due to the high number of fatal road traffic accidents and this pool is yet to be tapped.We report DDRT outcome in 294 patients (age: 36.5 ± 14.1 years; male:female, 200:94) between 2005 and 2012. All patients received single-dose rabbit-anti-thymocyte globulin for induction and steroids, calcineurin inhibitor, and mycophenolate mofetil/azathioprine for maintenance immunosuppression.Our retrospective study in 294 DDRT shows a fairly successful outcome. Over a mean follow-up of 3.93 years, patient and graft survival rates were 81.7% and 92.6%, respectively, with a median serum creatinine of 1.5 mg/dL. 20.7% had biopsy-proven acute rejection.Given the widespread organ shortage, DDRT has a potential to expand the donor pool and shorten the waiting list for RT, encouraging the use of this approach even in low-income countries. Aggressive donor management, increasing public awareness about the concept of organ donation, good communication between clinician and the family members, and a well-trained team of transplant coordinators can help in improving the number of organ donations.

Different strategies are being tried to induce transplant tolerance in clinical settings; however, none of them are both safe and effective. Mesenchymal stem cells have been found to be potent immunomodulators and immunosuppressants. We discuss in this review different sources of mesenchymal stem cells and the potent role of adipose tissue-derived mesenchymal stem cells in induction of transplant tolerance including when to use them and how to use them for achieving the Utopian dream of transplant tolerance.

Transplantation tolerance is still a Utopian dream for many transplanters. Mesenchymal stem cells (MSC) have shown immuno-modulatory and tolerogenic effects in experimental models. We present a 29-year-old male with end stage renal disease (ESRD) who was transplanted with HLA 4/6 matched kidney from 51-year-old father in June 2010 preceded by co-infusion of donor-adipose tissue derived mesenchymal stem cells (AD-MSC) and bone marrow derived hematopoietic stem cells (BM-HSC) under non-myeloablative conditioning for deleting rejecting T and B-cells. He has maintained fairly stable graft function with serum creatinine (SCr) between 1.5 and 1.8 mg/dL at 3 years post-transplant with absence of donor specific antibodies (DSA), normal protocol graft biopsy, and peripheral T-regulatory cell levels (pTregs) (CD127low/−CD25highCD4+) of 4.57% on zero immunosuppression since 6 months.

Kidney paired donation (KPD) is a rapidly growing modality for facilitating living donor kidney transplantation (LDKTx) for patients who are incompatible with their healthy, willing and living donor. The impact of donor-recipient age difference on long and short-term graft and patient survivals in LDKTx is still uncertain.A total of 1502 LDKTx recipients who received regular follow-up in our center from 1999 to 2012 were studied. Donor-recipient age difference was divided into subgroups (donor-recipient 0-10, 11-20, 0-20, 21-30, 31-40, and 21-40 years). Outcome measures included death censored graft, patient survival and acute rejection rate.The 1-, 5-, 10-year patient survival of the donor-recipient age difference ≤20 years group showed no difference compared with the age difference20 years group (94.5%, 83.2%, 71.9% and 95.2%, 86%, 77.8%, p = 0.053). The 1-, 5-, 10-year graft survival of the donor-recipient age difference ≤20 years group showed no difference compared with the age difference20 years group (94.6%, 81.6%, 72.1% and 94%, 80%, 72.2%, p = 0.989). The rejection were also similar (17.5% vs. 16.5%, p 0.05). There was no statistically significant difference in graft survival and acute rejection rate in all subgroups.Older donors (usually within families) are not associated with worse outcome is reassuring. KPD should not be prohibited due to high donor-recipient age difference, when size of donor pool is small as in single center KPD program.

Tumor lysis syndrome (TLS) is well described treatment related oncologic emergency with hyperuricemia being a cardinal sign of it leading to acute uric acid nephropathy. But spontaneous occurrence of TLS has occasionally been described in the literature. This spontaneous tumor lysis syndrome (STLS) is unusual cause for acute kidney injury (AKI) and a very uncommon initial presentation of lymphoma. AKI occurring in the setting of STLS has very poor outcome as it was not possible to institute preventive measures leading to very high mortality. We report a case of non-Hodgkin's lymphoma presenting with severe hyperuricemia with AKI. Our case stresses the importance of rapid diagnosis and treatment of AKI due to STLS which helps in early renal recovery. With prompt and timely initiation of hemodialysis and other supportive measures, renal failure and prognosis can be improved.

The presence of positive anti-human, globulin-enhanced, complement-dependent cytotoxicity crossmatches (AHG-CDC-XM) generally has been considered as a contraindication to kidney transplantation (KTx). Flow cytometry crossmatch (FCXM) and solid phase antibody screening are most sensitive and specific methods for immunological assessment. The outcome effect of donor-specific antibody (DSA) positive by Luminexx platform and CDCXM negative has been evaluated, but not the outcome of CDCXM positive and DSA negative. This is a case report describing KTx in a patient with pre-transplant positive AHG-CDC-XM but negative FCXM and without detectable DSA by Luminexx single antigen beads. CDCXM, FCXM, DSA were negative after transplantation, and kidney allograft biopsy did not show immune injury with negative C4d. Our report suggests that KTx with positive AHG-CDC-XM can be considered if FCXM and DSA were negative with careful immunological monitoring after transplantation. In our case, the IgM-antibodies were responsible for the positive AHG-CDC-XM result. The patient with positive CDC XM has a good outcome in the absence of DSA. Further work is needed to determine under what circumstances CDCXM positive transplants can be performed with FCXM and DSA negative.

We present a study of up-regulation of genes responsible for pancreatic development in glucose-sensitive insulin-secreting mesenchymal stem cells (IS-MSC) generated and differentiated from human adipose tissue (h-AD), with use of our specific differentiation media and without use of any xenogenic material. Anterior wall abdominal fat was collected from 56 volunteers and cultured in self-designed proliferation medium for 10 days. Cells were harvested by trypsinization and differentiated into insulin-expressing cells using self-designed differentiation medium for 3 days followed by evaluation for transcriptional factors Pax-6, Ipf-1, Isl-1, C-peptide and insulin secretion. Generated IS-MSC showed expression of Pax-6, Pdx-6 and Isl-1. Non-differentiated MSC as well as their further culture in absence of differentiation medium were used as negative controls. Generated 56 IS-MSC cell-lines were glucose responsive i.e. mean C-Peptide and insulin secretion levels were measured 0.41 ng/ml and 13.13 μU/ml, respectively, in absence of glucose which rose to 1.18 ng/ml and 83.42 μU/ml, respectively, following glucose challenge (p < 0.001). The mean rise in C-peptide and insulin secretion levels was 2.88 and 6.35 fold, respectively. To conclude insulin-secreting h-AD-MSC can be generated safely and effectively with application of specific differentiation media without xenogeneic material/any genetic modification, showing expression of transcriptional factors Pax-6, Ipf-1 and Isl-1.

Down syndrome is one of the most common genetic causes of learning disabilities in children. Although the incidence of renal and urological involvement in Down syndrome is not very common, monitoring of patients with Down syndrome for renal diseases should be done regularly as patient’s age into the second and third decades. With increased survival, it appears that a growing number of these patients present with chronic renal failure. Down syndrome patients are apparently not suited for peritoneal dialysis because of lacking cooperation. This procedure can be prone to failure, mainly because of an increased risk of peritonitis. Handling such patients especially those on peritoneal dialysis is challenging. Here we report a case of Down syndrome with end-stage renal disease treated with hemodialysis for 6 months. To the best of our knowledge and current literature review this is the first case report of a patient with Down syndrome undergoing hemodialysis.

BACKGROUND: We undertook this study to define the role of stem cell transplantation (SCT) versus donor-specific transfusion (DST) in tolerance induction and sustenance in living donor renal transplantation (LDRT). METHODS: In this prospective three-armed trial in LDRT with 13 patients each in demographically well-balanced groups, tolerance induction protocol (TIP) was used with SCT in group 1, DST in group 2, and no induction in group 3. Tolerance induction protocol consisted of SCT/DST under conditioning with bortezomib, methylprednisone, rituximab, and rabbit antithymocyte globulin. Transplantation was performed with prednisone in groups 1 and 2 and with triple immunosuppression in group 3, if lymphocyte/flow crossmatch was negative; and if donor-specific antibodies (DSAs) were absent in the first 2 groups. Posttransplant monitoring included serum creatinine (SCr), peripheral T-regulatory cells (pTregs)(127/CD4+/25), and DSA for groups 1 and 2; DSA was eliminated in group 3. Rescue IS was started with rise of SCr/DSA/ rejection. RESULTS: Tolerance induction protocol was safe. Over a mean follow-up of 2 years, no patient/graft was lost in groups 1 and 2. One patient of group 3 lost graft to noncompliance. Protocol biopsies were unremarkable. Rejections were noted in six patients of group 1, five of group 2, and seven of group 3. Donor-specific antibodies were elevated in three patients of both groups. Mean SCr of all groups was similar; however, pTregs were increased posttransplant in groups 1 and 2 versus group 3. Group 1 had sustained rise in pTregs. CONCLUSION: Stem cell transplantation and DST are useful for immunosuppression minimization in LDRT with sustained generation of pTregs with SCT.

Although end-stage renal disease (ESRD) related to AA amyloidosis nephropathy secondary to tuberculosis is most common in our country, there are limited data concerning patient and graft outcome after renal transplantation (RTx). To the best of our knowledge, this is the first report of RTx in ESRD patient with secondary amyloidosis due to tuberculosis from India. A 30-year-old female with past history of pulmonary tuberculosis 3 years back was admitted with complaint of gradually progressive pedal oedema and nausea for 3 months. Renal biopsy was suggestive of secondary renal amyloidosis with vascular involvement and chronic tubulointerstitial involvement. She was transplanted with kidney from her 28-year-old brother with 3/6 human leukocyte antigen match. She had immediate good graft function without any perioperative complications (cardiovascular, infections, rejection and delayed graft function). She was discharged with serum creatinine of 0.8 mg/dL. Her last serum creatinine level was 0.9 mg/dL with cyclosporine level of 100 mg/dL at 9-month followup without any medical or surgical complication. The quality of life also improved after transplantation. With careful selection, ESRD patients with secondary amyloidosis due to tuberculosis are eligible for RTx with favorable outcome and improved quality of life.

Churg-Strauss syndrome (CSS) also called allergic granulomatosis and angiitis is a multisystem disorder. Churg-Strauss syndrome is defined as an eosinophil-rich, granulomatous inflammation involving the respiratory tract, along with necrotizing vasculitis affecting small- to medium-sized vessels, and is associated with asthma and eosinophilia. Renal involvement in CSS varies from 26 to 88 % but is usually of mild to moderate stage, and advanced renal failure is uncommon. We encountered an unusual case of 27-year-old man with asthma and primary focal segmental glomerulosclerosis diagnosed as CSS showing myeloperoxidase anti-neutrophil cytoplasmic antibody-associated acute kidney injury with crescentic glomerulonephritis. Patient responded to steroid and cyclophosphamide. Over a follow-up of 2 months, he has no hematuria/eosinophilia and serum creatinine of 2.3 mg/dL has decreased to 1.7 mg/dL.

Economic constraints in operating an effective maintenance dialysis program leaves renal transplantation as the only viable option for end-stage renal disease patients in India. Kidney paired donation (KPD) is a rapidly growing modality for facilitating living donor (LD) transplantation for patients who are incompatible with their healthy, willing LD. The aim of our study was to report a single-center feasibilities and outcomes of KPD transplantation between 2000 and 2012. We performed KPD transplants in 70 recipients to avoid blood group incompatibility (n = 56) or to avoid a positive crossmatch (n = 14). Over a mean follow-up of 2.72 ± 2.96 years, one-, five- and ten-year patient survival were 94.6, 81, 81 %, and death-censored graft survival was 96.4, 90.2, 90.2 %, respectively. Ten percent of patients were lost, mainly due to infections (n = 4). There was 14.2 % biopsy-proven acute rejection, and 5.7 % interstitial fibrosis with tubular atrophy eventually leading to graft loss. The incidences of acute rejection, patient/graft survival rates were acceptable in our KPD program and, therefore, we believe it should be encouraged. These findings are valuable for encouraging participation of KPD pairs and transplant centers in national KPD program. It should be promoted in centers with low-deceased donor transplantation. Our study findings are relevant in the context of Indian government amending the Transplantation of Human Organs Act to encourage national KPD program. To our knowledge, it is largest single-center report from India.

Renal transplant patients are at high risk of developing various infections causing morbidity and mortality. Invasive fungal infection has been recognized as a significant complication of organ transplantation. The major fungal infections in these patients are due to candida, aspergillus and mucormycosis. However, infection because of infrequently encountered fungi like hyaline molds, dematiaceous filamentous fungi and zygomycetes are increasing in immunocompromised hosts. Dematiaceous fungi are recognized pathogens in organ transplant recipients with skin and soft tissue infection. We report the case of a 37-year-old man, a renal transplant recipient who developed an asymptomatic dematiaceous fungal infection in submandibular salivary gland. He recovered after excision and antifungal therapy.