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Purpose We reviewed the clinical experience of kidney transplant recipients diagnosed with severe acute respiratory syndrome coronavirus 2 infection in order to understand the impact of the current coronavirus disease 2019 (COVID-19) pandemic infection on transplant recipients. Given that early reports from heavily affected areas demonstrated a very high mortality rate amongst kidney transplant recipients, ranging between 30% and 40%, we sought to evaluate outcomes at a center with a high burden of cases but not experiencing acute crisis due to COVID-19. Procedures In this single center retrospective observational study, medical records of all kidney transplant recipients at the UCLA Medical Center were reviewed for a diagnosis of COVID-19 by polymerase chain reaction, followed by chart review to determine kidney transplant characteristics and clinical course. Main findings A total of 41 kidney transplant recipients were identified with COVID-19 positive polymerase chain reaction. Recipients had been transplanted for a median of 47 months before diagnosis. The large proportion of infected individuals were minorities (Hispanic 65.9%, black 14.6%), on prednisone, tacrolimus, and mycophenolate mofetil (95.1%, 87.8%, and 87.8%, respectively), and had excellent allograft function (median 1.25 mg/dL). The most common presenting symptoms were fever, dyspnea, or cough. Most patients were hospitalized (63.4%); mortality was 9.8% and occurred only in patients in the intensive care unit. The most common treatment was reduction or removal of antimetabolite (77.8%). Approximately 26.9% presented with AKI. Conclusions COVID-19 infection in kidney transplant recipients results in a higher rate of hospitalization and mortality than in the general population. In an area with a high number of infections, the mortality rate was lower compared with earlier reports from areas experiencing early surge and strain on the medical system. Minorities were disproportionately affected. Future studies are needed to determine optimal approach to treatment and management of immunosuppression in kidney transplant recipients with COVID-19 infection.

Hyperphosphatemia may arise from various conditions including exogenous ingestion, extracellular shifts due to cell death or alterations in acid-base status, increased bone resorption, hormonal dysregulations leading to reduced renal excretion, reduced kidney function, or faulty measurement techniques. We herein present a case of a young pregnant woman who presented with mild acute kidney injury (AKI), invasive mucormycosis receiving liposomal amphotericin, and hyperphosphatemia out of proportion to the degree of kidney injury. While the patient was given routine phosphate-binding agent by her primary care team for presumed AKI-associated hyperphosphatemia, a full investigation by the renal consulting team for contributing factors other than kidney injury revealed that she actually had pseudohyperphosphatemia associated with the use of liposomal amphotericin. Erroneous treatment of pseudohyperphosphatemia may have been detrimental to this pregnant patient. A literature review for conditions associated with pseudohyperphosphatemia other than the use of liposomal amphotericin will be discussed.

Hemolysis, vaso-occlusion, and ischemia reperfusion represent the clinical hallmarks of sickle cell disease (SCD). Renal involvement occurs commonly in SCD. Its manifestations range from the near universal findings of hyposthenuria to various tubular and glomerular functional and anatomical abnormalities—commonly referred to as sickle cell nephropathy. With increasing longevity of SCD patients, overt chronic kidney disease (CKD) and end-stage renal disease have increasingly been observed. Possible risk factors or genetic modifiers are associated with the development and/or progression of CKD. Preventive measures and therapeutic options have been developed.

The prevalence of pain has been reported to be >60–70% among patients with advanced and end-stage kidney disease. Although the underlying etiologies of pain may vary, pain per se has been linked to lower quality of life and depression. The latter is of great concern given its known association with reduced survival among patients with end-stage kidney disease. We herein discuss and update the management of pain in patients with chronic kidney disease with and without requirement for renal replacement therapy with the focus on optimizing pain control while minimizing therapy-induced complications.

BackgroundBK virus infection remains an important cause of loss of allograft function after kidney transplantation. We sought to determine whether polyfunctional T cells secreting multiple cytokines simultaneously, which have been shown to be associated with viral control, could be detected early after start of BK viremia, which would provide insight into the mechanism of successful antiviral control.MethodsPeripheral blood mononuclear cells collected during episodes of BK viral replication were evaluated by multiparameter flow cytometry after stimulation by overlapping peptide pools of BK virus antigen to determine frequency of CD8+ and CD4+ T cells expressing 1 or more cytokines simultaneously, as well as markers of T-cell activation, exhaustion, and maturation.ResultsBK virus controllers, defined as those with episodes of BK viremia of 3 months or less, had an 11-fold increase in frequency of CD8+ polyfunctional T cells expressing multiple cytokines, as compared with patients with prolonged episodes of BK viremia. Patients with only low level BK viremia expressed low frequencies of polyfunctional T cells. Polyfunctional T cells were predominantly of the effector memory maturation subtype and expressed the cytotoxicity marker CD107a.ConclusionsNoninvasive techniques for immune assessment of peripheral blood can provide insight into the mechanism of control of BK virus replication and may allow for future patient risk stratification and customization of immune suppression at the onset of BK viremia.

While some electrolyte disturbances are immediately life-threatening and must be emergently treated, others may be delayed without immediate adverse consequences. We discuss a patient with alcoholism and diabetes mellitus type 2 who presented with volume depletion and multiple life-threatening electrolyte and metabolic derangements including severe hyponatremia (serum sodium concentration [SNa] 107 mEq/L), hypophosphatemia (“undetectable,” SAG] 37) and hypocalcemia (ionized calcium 4.0 mg/dL), mild hypomagnesemia (1.6 mg/dL), and electrocardiogram with prolonged QTc. Following two liters of normal saline and associated increase in SNa by 4 mEq/L and serum osmolality by 2.4 mosm/Kg, renal service was consulted. We were challenged with minimizing the correction of SNa (or effective serum osmolality) to avoid the osmotic demyelinating syndrome while replacing volume, potassium, phosphorus, calcium, and magnesium and concurrently treating DKA. Our management plan was further complicated by an episode of significant aquaresis. A stepwise approach was strategized to prioritize and correct all disturbances with considerations that the treatment of one condition could affect or directly worsen another. The current case demonstrates that a thorough understanding of electrolyte physiology is required in managing complex electrolyte disturbances to avoid disastrous outcomes.

Retroperitoneal fibrosis (RPF) is a condition characterized by chronic inflammatory and fibrotic changes in the retroperitoneum that can lead to serious complications including kidney failure, mesenteric and limb ischemia, and deep venous thrombosis among others. Affected individuals may present with nonspecific symptomology that would require a high clinical index of suspicion for prompt diagnosis. We herein discuss a case of a young African-American man with recurrent deep venous thrombosis who presents with a 4-week history of constant aching pain of abdomen and back and kidney failure. Initial noncontrast computed tomogram (CT) only revealed mild bilateral hydroureteronephrosis with inflammatory changes but without obvious mass or lymphadenopathy. At the insistence of the renal consulting team to rule out RPF, a CT-urogram was performed which revealed an infiltrative mass encasing the aorta, inferior vena cava, and common iliac vessels. Laparoscopic biopsy revealed dense fibroadipose tissue, lymphocytic aggregates, focal scattered IgG4-positive plasma cells, and fibrin deposition. Patient underwent bilateral nephrostomy placement and empirical corticosteroid therapy with resolution of kidney failure. Our case illustrates a classic presentation of RPF with relatively benign findings on noncontrast CT that could have been missed if clinicians did not keep a high index of suspicion for the condition.

Cisplatin is known to induce Fanconi syndrome and renal salt wasting (RSW). RSW typically only requires transient normal saline (NS) support. We report a severe RSW case that required 12 liters of 3% saline. A 57-year-old woman with limited stage small cell cancer was admitted for cisplatin (80 mg/m2) and etoposide (100 mg/m2) therapy. Patient’s serum sodium (SNa) decreased from 138 to 133 and 125 mEq/L within 24 and 48 hours of cisplatin therapy, respectively. A diagnosis of syndrome of inappropriate antidiuretic hormone secretion (SIADH) was initially made. Despite free water restriction, patient’s SNa continued to decrease in association with acute onset of headaches, nausea, and dizziness. Three percent saline (3%S) infusion with rates up to 1400 mL/day was required to correct and maintain SNa at 135 mEq/L. Studies to evaluate Fanconi syndrome revealed hypophosphatemia and glucosuria in the absence of serum hyperglycemia. The natriuresis slowed down by 2.5 weeks, but 3%S support was continued for a total volume of 12 liters over 3.5 weeks. Attempts of questionable benefits to slow down glomerular filtration included the administration of ibuprofen and benazepril. To our knowledge, this is the most severe case of RSW ever reported with cisplatin.

Osmotic demyelination syndrome (ODS) is a complication generally associated with overly rapid correction of hyponatremia. Traditionally, nephrologists have been trained to focus solely on limiting the correction rate. However, there is accumulating evidence to suggest that the prevention of ODS is beyond achieving slow correction rates.We (1) reviewed the literature for glial intracellular protective alterations during hyperosmolar stress, a state presumed equivalent to the rapid correction of hyponatremia, and (2) analyzed all available hyponatremia-associated ODS cases from PubMed for possible contributing factors including correction rates and concurrent metabolic disturbances involving hypokalemia, hypophosphatemia, hypomagnesemia, and/or hypoglycemia.In response to acute hyperosmolar stress, glial cells undergo immediate extracellular free water shift, followed by active intracellular Na(+), K(+) and amino acid uptake, and eventual idiogenic osmoles synthesis. At minimum, protective mechanisms require K(+), Mg(2+), phosphate, amino acids, and glucose. There were 158 cases of hyponatremia-associated ODS where both correction rates and other metabolic factors were documented. Compared with the rapid correction group (0.5 mmol/L/h), the slow correction group (≤0.5 mmol/L/h) had a greater number of cases with concurrent hypokalemia (49.4 vs. 33.3 %, p = 0.04), and a greater number of cases with any concurrent metabolic derangements (55.8 vs. 38.3 %, p = 0.03).Glial cell minimizes volume changes and injury in response to hyperosmolar stress via mobilization and/or utilization of various electrolytes and metabolic factors. The prevention of ODS likely requires both minimization of correction rate and optimization of intracellular response during the correction phase when a sufficient supply of various factors is necessary.

In recipients of kidney transplants, the emergence of BK virus (BKV)-associated clinical syndromes, such as viruria, viremia, and BK nephropathy, coincided with the advent of potent immunosuppressive therapy. There is currently no standardized protocol for the management of BK viruria or viremia, or established BK nephropathy. Suggested risk factors for BKV replication and a literature overview on various treatment strategies for BKV-associated clinical syndromes are presented, followed by the authors' proposed approach for screening, monitoring, and treatment of post-transplant BKV infection.BKV infection can occur under all combinations of immunosuppressive therapy. Although both humoral and cellular immunity may be essential, BKV-specific T-cell immunity appears to play a pivotal role in controlling BKV replication. Monitoring BKV-specific immune response might prove useful in guiding therapeutic intervention. The beneficial effects of antiviral agents remain unclear. Development of T-cell or antibody-based vaccines against BKV is a subject of future research.In the absence of conclusive evidence that any particular immunosuppressive agent has a specific influence over another on BKV infection risk and the unclear benefit of antiviral agents, intensive monitoring of serum BKV using PCR and immunological containment of BKV replication should remain the mainstay of therapy. The routine recommendations of antiviral agents in the treatment of BKV-associated clinical syndromes await results of large prospective randomized trials.

Although magnesium is involved in a wide spectrum of vital functions in normal human physiology, the significance of hypomagnesemia and necessity for its treatment are under-recognized and underappreciated in clinical practice. In the current review, we first present an overview of the clinical significance of hypomagnesemia and normal magnesium metabolism, with a focus on renal magnesium handling. Subsequently, we review the literature for both congenital and acquired hypomagnesemic conditions that affect the various steps in normal magnesium metabolism. Finally, we present an approach to the routine evaluation and suggested management of hypomagnesemia.

The prevalence of obesity (body mass index ≥30 kg/m(2)) at the time of transplantation among kidney transplant recipients in the United States has doubled between 1987 and 2001 and continues to increase inexorably. Single-center and large registry studies in kidney transplant recipients demonstrated that high body mass index (BMI) at transplant is associated with increased risk of wound and surgical site infections, delayed graft function (DGF), acute rejection episodes, and graft loss, among others. Hence, in many centers, obese transplant candidates are denied a transplant based on their body mass index (BMI) alone. The impact of obesity on short- and long-term graft and patient outcomes after kidney transplantation are herein revisited, followed by the authors' proposed approach to evaluate and select obese transplant candidates for a kidney transplant. Suggested interventions to optimize the health of such candidates are also discussed.

Over the past decade, patients returning to dialysis after a failed transplant comprised of 5-10% of the annual number of dialysis initiations in the United States, whereas retransplant candidates account for 5.0-13% of the annual deceased donor wait-list additions. The United States Renal Data System (USRDS) database revealed a >3-fold increase in the annual adjusted death rates for patients returning to dialysis after graft loss compared with patients with a functioning allograft (9.4% vs. 2.8%, respectively). Continuation of low-dose immunosuppression to maintain residual allograft function has been suggested as a contributing factor, presumably via treatment-related infectious and cardiovascular complications among others. In contrast, a survival advantage in maintaining patients on long-term immunosuppression after returning to peritoneal dialysis has also been suggested. Despite the significant number of patients requiring reinitiation of some form of renal replacement therapy after a failed transplant and the increasing evidence suggesting their high mortality and morbidity rates, management of the failed allograft in these patients has received little attention. This article presents an overview of the literature on the management of immunosuppression after allograft failure, a brief review on the pros and cons of allograft nephrectomy, and the authors' opinions on the management of immunosuppression in patients with a failed kidney allograft.

We found in our present study that lithium (Li(+)) induced the expression of endogenous c-Ret, a tyrosine kinase receptor, in murine inner medullary collecting duct (mIMCD-3) cells. Delineation of the promoter region required for the effect of Li(+) identified a positive regulatory element within 180bp upstream of the transcription initiation site. This region contained three putative GC-rich Sp1 binding sites found to be essential for c-Ret induction by Li(+). The effect of Li(+) was mediated through glycogen synthase kinase 3β (GSK-3β) inhibition, although there was no biding site for T cell factor/lymphoid enhancer factor (TCF/LEF) in the 180bp. We found that Li(+) activated the mammalian target of rapamycin (mTOR) pathway via GSK-3β in these cells, and the effect of Li(+) to induce c-Ret was amenable to the inhibitory effect of the mTOR inhibitor, rapamycin. We also found that alterations in both cellular β-catenin levels and mTOR activities affected the effect of Li(+) on c-Ret transcription in a cooperative manner. In summary, our results show that Li(+) can induce c-Ret expression in mIMCD-3 cells through both β-catenin- and mTOR-dependent pathways downstream of GSK-3β inhibition, which act synergistically on the GC-rich Sp1 binding elements in the promoter region.

Important advances in immunosuppressive therapy and refinement in surgical techniques have allowed renal transplantation to become the treatment of choice for virtually all suitable candidates with end-stage renal disease. Compared to dialysis, kidney transplantation improves both patient survival and quality of life and, over time, can reduce the total cost of medical care. It must be noted, however, that although the risk of death in the first year after transplantation is

Purpose of review Acute and chronic kidney injury following orthotopic liver transplantation (OLT) is associated with increased morbidity and mortality. With the increasing longevity of liver transplant recipients, chronic kidney disease (CKD) has become an increasingly prevalent complication among long-term survivors. This article provides an overview of the literature on suggested risk factors for acute and CKD following OLT and a discussion of an approach to their medical management. Recent findings In OLT candidates with pretransplant renal dysfunction, the use of interleukin-2 receptor blockers or antithymocyte globulin induction therapy in conjunction with delayed introduction of calcineurin inhibitors may preserve early renal function. In long-term stable OLT recipients with established calcineurin inhibitor nephrotoxicity, calcineurin inhibitor minimization or withdrawal protocols may halt or ameliorate renal dysfunction without compromising patient and graft survival. However, large-scale, multicenter, randomized controlled trials are still needed. Summary The occurrence of acute kidney injury is common immediately after OLT, whereas the incidence of CKD and end-stage renal disease increases with time. Identifying patients at risk for acute kidney injury and CKD following OLT and early implementation of measures to preserve, halt, or ameliorate the progression of renal dysfunction should be an integral part in the management of OLT recipients.

Posttransplant malignancy developing in an allograft is an uncommon complication of organ transplantation. The tumor may represent malignant transformation of donor or recipient cells that were previously normal, metastatic malignancy of recipient origin or malignancy transmitted from organ donor to recipient. Establishing the origin of the malignancy is critical to treatment algorithms. It is generally believed allograft removal and immunosuppression withdrawal will lead to resolution of transmitted malignancies in cases where the renal allograft is the origin. We report a male patient who developed metastatic ovarian malignancy secondary to donor transmission.

Pain has been reported to be a common problem in the general population and end-stage renal disease (ESRD) patients. Although similar data for pre-ESRD patients are lacking, we recently reported that the prevalence of pain is also very high (>70%) among pre-ESRD patients at a Los Angeles County tertiary referral centre. The high prevalence of pain in the CKD population is particularly concerning because pain has been shown to be associated with poor quality of life. Of greater concern, poor quality of life, at least in dialysis patients, has been shown to be associated with poor survival. We herein discuss the pathophysiology of common pain conditions, review a commonly accepted approach to the management of pain in the general population, and discuss analgesic-induced renal complications and therapeutic issues specific for patients with reduced renal function.

Su Su Hline1, Phuong-Truc T Pham2, Phuong-Thu T Pham3, May H Aung1, Phuong-Mai T Pham4, Phuong-Chi T Pham11Olive View-UCLA Medical Center, Department of Medicine, Nephrology Division, Sylmar, CA, USA; 2Pennsylvania State Worthington Scranton, Dunmore, PA, USA; 3David Geffen School of Medicine at UCLA Medical Center, Los Angeles, CA, USA; 4Mather VA Medical Center, Mather, CA, USAAbstract: Hyponatremia is one of the most common electrolyte abnormalities linked to adverse outcomes and increased mortality in hospitalized patients. While the differential diagnosis for hyponatremia is diverse, most cases stem from arginine vasopressin (AVP) dysregulation, where hypoosmolality fails to suppress AVP synthesis and release. The physiological effects of AVP are currently known to depend on its interaction with any of 3 receptor subtypes V1A, V2, and V1B. Activation of V2 by AVP is the key in renal water regulation and maintenance of total body volume and plasma tonicity. Despite the long-recognized problem with excess AVP in euvolemic and hypervolemic hyponatremia, traditional therapeutic options have relied on nonspecific and potentially problematic strategies. More recently, a new class of drugs, introduced as “aquaretics,” has gained great attention among clinicians because of its ability to correct hyponatremia via direct competitive inhibition of AVP at V2 receptors to induce renal electrolyte-free water excretion. In this paper, we aim to review available clinical data on the only FDA-approved aquaretic, dual V1A/V2 receptor antagonist conivaptan, discuss its clinical indications, efficacy, safety profile, and comment on its clinical limitations.Keywords: conivaptan, hyponatremia, euvolemia, hypervolemia, AVP, AVP receptor antagonist

This article presents an overview of the literature on the current diagnostic criteria for new onset diabetes mellitus after transplantation (NODAT) and discusses suggested risk factors for the development of NODAT, its potential pathogenic mechanisms, and its impact on post-transplant outcomes after solid organ transplantation. Suggested guidelines for early identification and management of NODAT are also discussed.

Advances in immunosuppressive therapy and refinement in surgical techniques have allowed pancreas after kidney (PAK) transplantation to become a viable therapeutic option for patients with brittle type I diabetic recipients of a living donor or previous deceased kidney alone transplant. Although maintenance immunosuppressive therapy is not significantly changed after the addition of a pancreas, a temporary booster in immunosuppressive therapy and an increase in the dose of calcineurin inhibitor (CNI) are required after PAK transplantation. The latter has been implicated in the observed variable decline in kidney allograft function. We herein report two cases of kidney allograft dysfunction following PAK transplant due to biopsy-proven transplant, thrombotic microangiopathy (TMA). Whether PAK transplantation pre-disposes a subset of patients to the development of post-transplant TMA is not known. Diagnostic kidney biopsies should be considered in PAK transplant recipients with worsening kidney allograft function.

Hypomagnesemia has been reported to occur at an increased frequency among patients with type 2 diabetes compared with their counterparts without diabetes. Despite numerous reports linking hypomagnesemia to chronic diabetic complications, attention to this issue is poor among clinicians. This article reviews the literature on the metabolism of magnesium, incidence of hypomagnesemia in patients with type 2 diabetes, implicated contributing factors, and associated complications. Hypomagnesemia occurs at an incidence of 13.5 to 47.7% among patients with type 2 diabetes. Poor dietary intake, autonomic dysfunction, altered insulin metabolism, glomerular hyperfiltration, osmotic diuresis, recurrent metabolic acidosis, hypophosphatemia, and hypokalemia may be contributory. Hypomagnesemia has been linked to poor glycemic control, coronary artery diseases, hypertension, diabetic retinopathy, nephropathy, neuropathy, and foot ulcerations. The increased incidence of hypomagnesemia among patients with type 2 diabetes presumably is multifactorial. Because current data suggest adverse outcomes in association with hypomagnesemia, it is prudent to monitor magnesium routinely in this patient population and treat the condition whenever possible.

Sickle cell nephropathy (SCN) encompasses a spectrum of renal functional and structural abnormalities that begins in childhood and may progress to advanced CKD or ESRD by early or late adulthood. Although SCN has traditionally been attributed to the consequences of a viscosity-vaso-occlusive process, it has increasingly been recognized that hemolysis-endothelial dysfunction may play an important contributory role. Regardless of the predominant pathogenic mechanisms, well-described clinicopathological manifestations of SCN include impaired urinary concentrating ability, impaired renal acidification and potassium secretion, hematuria, proteinuria, focal segmental glomerulosclerosis and progressive renal disease, among others. Progressive CKD may develop as a consequence of irreversible glomerular and tubulointerstitial damage. The range of kidney abnormalities associated with sickle cell disease (SCD) is wide, and the underlying pathophysiologic mechanisms are varied. Therapeutic measures to prevent or alleviate kidney complications associated with SCD may have value.

Scleroderma renal crisis (SRC) can lead to end-stage renal disease (ESRD) and subsequent need for dialysis and/or renal transplantation. We review all reported cases of renal transplantations in scleroderma patients from PubMed search, present UNOS data on transplant outcomes, and identify predictors for allograft SRC. Of the five cases with recurrent SRC, all developed ESRD within a year of onset of native kidney SRC, whereas none of those who developed ESRD more than 1-2 years after the onset of SRC developed recurrence. Anemia preceded allograft SRC in two cases, pericardial effusion in one, and skin tightening in two others. UNOS data (October 1987-July 2004) documented 260 transplants performed for the renal diagnosis of scleroderma, with a 5-year graft survival rate of 56.7%. The risk for allograft SRC recurrence appears to correlate with early native renal function loss following the onset of SRC. Recurrent SRC in the allograft may be heralded by multiple clinical markers known to be predictive of severe scleroderma, including progression of diffuse skin thickening, new-onset anemia and cardiac complications.

Genetic studies indicated that mutations of the chloride channel CLC-5 in the kidney are responsible for a group of clinical disorders, collectively called Dent's disease. In the kidney, CLC-5 was found to be expressed in the proximal tubule, medullary thick ascending limb (mTAL) of loop of Henle, and intercalated cells of the collecting tubule. In proximal tubular cells, CLC-5 was found to play an important role in receptor-mediated endocytosis. However, the functional roles of CLC-5 in mTAL and collecting tubules remain unclear. Because mTAL is normally exposed to a hypertonic environment, we aimed to examine the effect of hypertonicity on CLC-5 expression in this nephron segment. Our studies revealed that exposure to hypertonicity (up to 550 mosM) increased CLC-5 mRNA and protein levels in a murine mTAL cell line (MTAL) but not in an opossum kidney (OK) proximal tubular cell line. A similar effect was also found in mouse kidneys, where CLC-5 expression was enhanced in renal medulla, but not cortex, after 48 h of water deprivation. We also tested the effect of hypertonicity on endocytotic activity and found that exposure to hypertonicity caused a significant decrease in cellular uptake of FITC-labeled albumin in OK but not in MTAL cells. Our results suggest that CLC-5 expression is upregulated by hypertonicity in mTAL cells but not in proximal tubular cells. We speculate that the increased CLC-5 levels in mTAL may serve to maintain the endocytotic activity in a hypertonic environment.

Background Pulmonary toxicity has recently been recognized as a potentially serious complication associated with sirolimus therapy. We further detail this condition on the basis of our own cases and those reported in the literature. Methods We report three cases of suspected sirolimus-induced pulmonary toxicity that occurred in three renal transplant recipients and searched PubMed for all previously reported cases. Results Including our current cases, 43 patients with sirolimus-induced pulmonary toxicity have now been reported. Clinical data were incomplete in 28 cases. Analysis of available data for 15 patients revealed that the most commonly presenting symptoms were dyspnea on exertion and dry cough followed by fatigue and fever. Chest radiographs and high-resolution computed tomography scans commonly revealed bilateral patchy or diffuse alveolo-interstitial infiltrates. Bronchoalveolar fluid analysis and lung biopsy in selected case reports revealed several distinct histologic features, including lymphocytic alveolitis, lymphocytic interstitial pneumonitis, bronchoalveolar obliterans organizing pneumonia, focal fibrosis, pulmonary alveolar hemorrhage, or a combination thereof. The diagnosis of sirolimus-associated pulmonary toxicity was made after an exhaustive work-up to exclude infectious causes and other pulmonary disease. Sirolimus discontinuation or dose reduction resulted in clinical and radiologic improvement in all 15 patients within 3 weeks. Conclusion The temporal relationship between sirolimus exposure and onset of pulmonary symptoms in the absence of infectious causes and other alternative pulmonary disease and the associated clinical and radiologic improvement after its cessation suggests a causal relationship. Because the use of sirolimus in organ transplantation has become more widespread, clinicians must remain vigilant to its potential pulmonary complication.

Chronic indwelling catheters have been reported to be associated with membranoproliferative glomerulonephritis (MPGN)viathe activation of the classical complement pathway in association with bacterial infections such as coagulase negative staphylococcus. We herein provide supporting evidence for the direct causal relationship between chronic catheter infections and MPGNviaa case of recurrent MPGN associated with recurrent catheter infections used for total parenteral nutrition (TPN) in a man with short gut syndrome. We also present a literature review of similar cases and identify common clinical manifestations that may serve to aid clinicians in the early identification of MPGN associated with infected central venous catheterization orvice versa. The importance of routine monitoring of kidney function and urinalysis among patients with chronic central venous catheterization is highlighted as kidney injury mayheraldor coincide with overtly infected chronic indwelling central venous catheters.

Background Advanced fibrosis or cirrhosis is still regarded as a contraindication for kidney transplantation alone by most centers. The value of aminotransferase to platelet ratio index (APRI) and other non-invasive markers has been less studied in hepatitis C virus (HCV)-positive patients with concurrent end-stage renal disease to predict hepatic fibrosis. Can these be used to effectively decrease the number of biopsies done in these patients being evaluated for transplantation? Methods Our study population included 255 patients with liver biopsy data. All patient information was collected and reviewed from medical records. The diagnostic accuracy of the predictive models was analyzed by calculating sensitivity, specificity, positive predictive value and negative predictive value. Results The variables associated with F3-F4 were aspartate aminotransferase (P = 0.007), bilirubin (P ≤ 0.001), platelet count (P = 0.01) and APRI (P ≤ 0.001). The use of any one laboratory abnormality to predict liver biopsy scores did not show high positive predictive values (22.6-72.7%). Having abnormal liver findings or cirrhosis on imaging was associated with high specificities (92.0-97.8%) but low sensitivities (31.4-42.9%). Using APRI levels of ≥0.40 and ≤0.95 as an indication for liver biopsy, 50% of patients with F3-F4 would have correctly avoided having a biopsy. However, 33% of patients with F3-F4 would have been mislabeled and not be indicated for biopsy. Conclusions Our data suggest that there may not currently be a simple and sufficiently accurate non-invasive test to replace liver biopsy in renal transplant workup for HCV-positive patients. The risks outweigh the benefits when it comes to using non-invasive markers like the APRI.

Early recognition and determination of the cause of renal failure in patients with ESLD can be difficult because of the potential interplay among various factors and the wide array of differential diagnoses. A systematic approach, however, assists clinicians to identify common and potentially reversible causes of ARF. It is crucial to distinguish patients with functional renal failure, such as HRS, from those with advanced irreversible renal disease. Isolated liver transplantation is the treatment of choice for the former, and CLKT may be a therapeutic option for the latter. Because of the ever-increasing shortage of donor organs, CLKT must be used judiciously. Kidney biopsy may resolve diagnostic dilemmas. Management of renal complications post-OLT remains a challenge for the physician caring for transplant patients. Modification of nephrotoxic immunosuppressive regimens to avoid postoperative ARF/CRI has met with variable results. Azathioprine has been used in place of cyclosporine. Therapy with polyclonal antilymphocyte preparations or anti-OKT3 monoclonal antibodies (Orthoclone) should be reserved for patients with delayed graft function and for the treatment of acute rejection. The routine use of these agents as prophylactic therapy is not recommended. Data on the impact of renal insufficiency on patient and allograft outcome are inconsistent. Nonetheless, the authors' literature review suggests that renal failure associated with sepsis and, except for patients with HRS, renal failure requiring dialysis are the most consistent features associated with a worse outcome. The need for preoperative or postoperative dialysis has no adverse effect on survival in patients with HRS. On long-term follow-up, despite a greater percentage of patients reaching ESRD in patients with HRS compared with their non-HRS counterparts, the overall outcome in patients with HRS following OLT is favorable. In patients with HRS requiring prolonged dialysis (i.e., greater than 4 weeks), however, irreversible renal failure may develop, necessitating CLKT. Ideally, timely referral of patients for OLT may avoid this complication and obviate the need for double organ transplantation.

Prior to the formal evaluation process, all potential transplant candidates are encouraged to attend a “patient education” session. At the meeting, patients are informed about the medical and surgical risks and benefits of renal transplantation, the necessity for frequent outpatient visits in the early postoperative period, the potential adverse effects of immunosuppression, and the importance of compliance with immunosuppressive therapy. The potential advan‐ tages and disadvantages of deceased versus living donor renal transplantation are discussed with the patients, and when possible, with their family members, significant others, and/or friends. Other issues that are addressed include prolonged waiting time for a deceased donor transplant due to the critical shortage of donor organ and adverse effects of waiting time on patient and graft survival. In addition, patients are forewarned that various medical and psychosocial conditions may preclude a patient from being a transplant candidate. Absolute and relative contraindications to kidney transplantation are outlined in table (1).

New-onset diabetes mellitus after transplantation (NODAT) is a serious and common complication following solid organ transplantation. NODAT has been reported in 2% to 53% of all solid organ transplants. Kidney transplant recipients who develop NODAT have variably been reported to be at increased risk of fatal and nonfatal cardiovascular events and other adverse outcomes including infection, reduced patient survival, graft rejection, and accelerated graft loss compared with those who do not develop diabetes. Limited clinical studies in liver, heart, and lung transplants similarly suggested that NODAT has an adverse impact on patient and graft outcomes. Early detection and management of NODAT must, therefore, be integrated into the treatment of transplant recipients. Studies investigating the best screening or predictive tool for identifying patients at risk for developing NODAT early after transplantation, however, are lacking. We review the clinical predictive values of fasting plasma glucose, oral glucose tolerance test, and A1C in assessing the risk for NODAT development and as a screening tool. Simple diabetes prediction models that incorporate clinical and/or metabolic risk factors (such as age, body mass index, hypertriglyceridemia, or metabolic syndrome) are also presented.

With the introduction of the MELD score for the allocation of orthotopic liver transplant (OLT) in February 2002, a striking 278% increase in the number of simultaneous liver-kidney transplants (SLKT) was observed during the 9-year period post-MELD when compared with the preceeding 9-year in the pre-MELD era (pre- vs.post-MELD era, n= 1049 vs. 2914, respectively) [1]. For OLT candidates with simultaneous end-stage kidney failure, SLKT is a well-established effective therapeutic option for virtually all suitable candidates.However, there have been no well-defined guidelines to determine whether a kidney transplant should be offered to OLT candidates who have chronic kidney disease (CKD) or prolonged acute kidney injury (AKI) secondary to hepatorenal syndrome (HRS) or acute tubular necrosis (ATN) while awaiting a liver transplant. Specific challenges in the decision making process include the accurate assessment of the degree of existing renal dysfunction in those with CKD and the prediction of the extent of renal function recovery in those with AKI with or without underlying CKD.

BK virus is a ubiquitous human virus with a peak incidence of primary infection in children 2-5 years of age and a seroprevalence rate of greater than 60-90% among the adult population worldwide. Following primary infection, BK virus preferentially establishes latency within the genitourinary tract and frequently reactivates in the setting of immunosuppression. In renal transplant recipients, BK virus is associated with a range of clinical syndromes including asymptomatic viruria with or without viremia, ureteral stenosis and obstruction, interstitial nephritis, and BK allograft nephropathy (BKN). BKN most commonly presents with an asymptomatic rise in serum creatinine between 2 to 60 months after engraftment (median 9 months). A definitive diagnosis requires an allograft biopsy. Over the last two decades, BKN has been recognized as an important cause of allograft dysfunction and graft loss in kidney transplant recipients. Nonetheless, there is currently no standardized protocol for the management of BK viremia or established BKN. In this article, a brief overview of the literature on the various treatment strategies for BK-associated clinical spectrum is presented followed by the authors’ suggested approach for posttransplant screening and monitoring for BK virus replication. Suggested treatment strategies are also discussed.

Background. Given the reported efficacy of mycophenolate mofetil (MMF) in the treatment of glomerular diseases, we question whether MMF can reduce the rate of renal allograft loss due to glomerular disease recurrence compared to azathioprine (AZA) as adjunctive therapy to cyclosporine (CSA)-based immunosuppression. Methods. This is a retrospective study based on the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) database designed to compare the Kaplan–Meier rates of graft loss due to disease recurrence stratified by primary renal diagnoses between recipients receiving CSA 1 AZA versus CSA 1 MMF. Recipients of primary kidney transplants (both deceased donor and living, related and unrelated) renal transplants performed between 1 January 1988 and 31 December 2007 with the primary renal diagnosis of IgA nephropathy (IgAN), membranous glomerulonephropathy (MGN), membranoproliferative glomerulonephropathy (MPGN), lupus nephritis (LN) or focal segmental glomerulosclerosis (FSGS) with a functioning allograft at discharge were included. Results. Seven thousand eight hundred and twenty-six recipients of primary deceased donor kidney transplants (DDKT) [CSA 1 AZA: IgAN (890), MGN (380), MPGN (193), LN (1324), FSGS (1314) and CSA 1 MMF: IgAN (855), MGN (614), MPGN (116), LN (715), FSGS (1425)] and 5498 recipients of living donor kidney transplants (LDKT) [CSA 1 AZA: IgAN (694), MGN (229), MPGN (100), LN (592), FSGS (654) and CSA 1 MMF: IgAN (1066), MGN (435), MPGN (89), LN (530), FSGS (1109)] were included in the analysis. At 10-year follow-up (mean duration was 5.6 to 6.7 6 1.8 years in DDKT and 6.2 to 7.4 6 1.7 years in LDKT), mean times of transplantation (era of transplantation) were: 1992 6 1.6 years and 2002 6 1.9 years for the CSA 1 AZA and CSA 1 MMF groups, respectively. There was no statistically significant difference in the Kaplan–Meier rates of graft loss due to disease recurrence of any glomerular disease studied between the CSA 1 AZA and CSA 1 MMF groups in either DDKT or LDKT recipients. Chi-square analysis revealed no statistically significant difference between the two immunosuppressive regimen groups in terms of age, gender and ethnic background. Conclusion. The OPTN/UNOS database revealed no difference in the rates of renal allograft loss due to disease recurrence of IgAN, MGN, MPGN, LN and FSGS among recipients receiving either CSA 1 AZA or CSA 1 MMF maintenance immunosuppressive therapy at 10-year follow-up.