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Australia's Indigenous people have high rates of chronic kidney disease and kidney failure. To define renal disease among these people, we reviewed 643 renal biopsies on Indigenous people across Australia, and compared them with 249 biopsies of non-Indigenous patients. The intent was to reach a consensus on pathological findings and terminology, quantify glomerular size, and establish and compare regional biopsy profiles. The relative population-adjusted biopsy frequencies were 16.9, 6.6, and 1, respectively, for Aboriginal people living remotely/very remotely, for Torres Strait Islander people, and for non-remote-living Aboriginal people. Indigenous people more often had heavy proteinuria and renal failure at biopsy. No single condition defined the Indigenous biopsies and, where biopsy rates were high, all common conditions were in absolute excess. Indigenous people were more often diabetic than non-Indigenous people, but diabetic changes were still present in fewer than half their biopsies. Their biopsies also had higher rates of segmental sclerosis, post-infectious glomerulonephritis, and mixed morphologies. Among the great excess of biopsies in remote/very remote Aborigines, females predominated, with younger age at biopsy and larger mean glomerular volumes. Glomerulomegaly characterized biopsies with mesangiopathic changes only, with IgA deposition, or with diabetic change, and with focal segmental glomerulosclerosis (FSGS). This review reveals great variations in biopsy rates and findings among Indigenous Australians, and findings refute the prevailing dogma that most indigenous renal disease is due to diabetes. Glomerulomegaly in remote/very remote Aboriginal people is probably due to nephron deficiency, in part related to low birth weight, and probably contributes to the increased susceptibility to kidney disease and the predisposition to FSGS.

Background: The healthcare burden due to chronic kidney disease has increased worldwide in the past decade. Elucidating the aetiology of chronic kidney disease may help in identifying strategies for prevention, both in the population and the Individual patient. Only a clinicopathological study can define the exact spectrum of chronic kidney disease since epidemiological studies have not shown a consistent aetiological profile. The histological evidence used to support the diagnosis varies with the degree to which renal biopsy is done. Renal biopsy is the gold standard in making an aetiological diagnosis in renal failure, but as a diagnostic tool in chronic kidney disease it is underutilized., Methods: This prospective study done at Christian Medical College, Vellore in southern India from 1998 to 2003 aimed to determine the aetiological profile of severe chronic kidney disease by analysing renal biopsies. The value of pre-renal biopsy clinical Judgement in predicting the histological diagnosis was also assessed. Patients with diabetic nephropathy were excluded from the study., Results: Four hundred and fifty-seven patients had evidence of chronic kidney disease as evidenced on biopsy as well as on clinical parameters. Three hundred and twenty-two of these patients (70.5%) had glomerulonephritis as the histological diagnosis. Fifty-five (12%) had Interstitial nephritis, 30 (6.6%) had hypertensive arteriosclerosis and 28 (6.1%) had metabolic nephropathies. The positive predictive value of a pre-biopsy clinical diagnosis in predicting interstitial nephritis was very low (33%). A large number of patients clinically diagnosed to have chronic interstitial nephritis had other aetiologies of chronic kidney disease., Conclusion: Glomerulonephritis was the most common cause of chronic kidney disease, not including diabetic nephropathy, followed by interstitial disease and benign arterionephrosclerosis. In patients with unidentified severe chronic kidney disease, renal biopsy provided an aetiological diagnosis.

Background: Urinary tract infection is the most common form of bacterial infection encountered in a renal transplant recipient. Studies explaining the long-term consequences of acute graft pyelonephritis (AGPN) are few., Methods: A total of 1022 consecutive renal allograft recipients were studied retrospectively over a period of 10 years for evidence of AGPN. These patients were classified into two groups according to the presence or absence of at least one AGPN episode. Only culture-proven infections were included in the study., Result: Of the 1022 renal transplant recipients, 169 patients (16.5%) developed AGPN. In the multivariate analysis with stepwise logistic regression, significant associations were observed between AGPN and placement of ureteric stent (odds ratio [OR]=4.6), urological malformations of native kidney (OR=2.1), cytomegalovirus (CMV) disease (OR=2.0), mycophenolate mofetil (MMF)-based regimen (OR=1.9), and acute rejection episodes (OR=1.5). However, age>40 years, female gender, induction therapy, anti-CD3 treatment, and hyperglycemia did not show such an association. In comparison with the non-AGPN group, these patients had a lower graft and patient survival (though it did not attain statistical significance). In the multivariate analysis using the Cox model for the entire study population, AGPN did not independently contribute to poor graft or patient survival., Conclusion: AGPN in the renal transplant setting is an ominous event, as these patients are also more prone to develop bacteremia, acute rejection, and CMV disease, which could then lead to poor graft and patient survival. Its association with MMF needs further clarification.

Background & Objectives: Presence of proteinuria is considered as an early marker of an increased risk of progressive kidney disease. Angiotensin converting enzyme (ACE) inhibitors (ACEi) and angiotensin II receptor blockers (ARB) treatment to persons with proteinuria and chronic kidney disease has been shown to decrease the progression to endstage renal disease. As the exact prevalence of proteinuria is not known in the general population, we undertook this study to estimate the same in a rural adult population in Vellore district, Tamil Nadu., Methods: A convenient sample of 5,043 adults was included. All individuals were tested for albuminuria by albumin dipstick examination in an untimed urine sample. Individuals who tested positive for albuminuria underwent a second dipstick examination after a gap of one week. Individuals with persistent albuminuria on the second dipstick examination underwent further evaluation which included medical history, physical examination, 24 h urine protein estimation, total serum protein and albumin estimation. Ultrasound of the abdomen was done in patients with renal failure and renal biopsy was performed in selected patients., Results: Of the total 5,043 individuals screened, 63.1 per cent were females. Mean age of the study population was 50.94 +/- 11.2 yr. First dipstick test identified 594 individuals positive for albuminuria. Repeat dipstick could be done in only 576, of whom 212 showed persistent albuminuria. Significant proteinuria was detected in 24 individuals of the 208 who had 24 h urine protein measured. Of these 24 patients, 3 were found to have chronic renal failure, 12 were presumed to have diabetic nephropathy clinically, one each had focal segmental glomerulosclerosis and biopsy proven diabetic nephropathy, and 7 patients had proteinuria of unknown aetiology., Interpretation & Conclusion: The prevalence of proteinuria in this adult rural population was 0.47 per cent (0.30-0.67%). The detection and treatment of chronic kidney disease in 24 individuals is bound to reduce the rate of decline of renal functions. Screening programme for proteinuria in different parts of country may be an effective measure to bring a decline in rate of progression of chronic kidney disease in general population.

Background: In the absence of a renal biopsy registry, there is a paucity of data on the renal disease pattern seen in India. This study reviews the changing pattern of renal disease seen at a single center over the last 30 yrs., Methods: Histopathological data of 5415 adequate native kidney biopsies performed on consecutive adult Indian patients presenting to our hospital from 1986-2002 were analyzed. This pathological demography classified according to the modified World Health Organization (WHO) classification was compared to the earlier published cohort collected from 1971-1985 (n=2827) to ascertain the changing trends., Results: The indications for renal biopsy were comparable between the cohorts and included nephrotic syndrome (65%), nephritic syndrome (13%) and chronic renal failure (10.2%). Primary glomerular disease accounted for 71% of all biopsies. Non-immunoglobulin A (IgA) mesangio proliferative glomerulonephritis as a group was the predominant pathology (20.2%), followed by idiopathic focal segmental glomerulosclerosis (FSGS) (17%), minimal change disease (MCD) (11.6%), membranous glomerulopathy (MN) (9.8%), IgA nephropathy (8.6%) and membranoproliferative glomerulonephritis (MPGN) (3.7%). Of the patients with secondary kidney diseases, lupus nephritis (6.5%), diabetic nephropathy (2.5%), interstitial nephropathy (2.5%) and benign nephrosclerosis (2.2%) were notable. During the 31 yrs of the study period, there was a steady increase in FSGS prevalence (p<0.001), MN (p<0.0001), and post infectious glomerulonephritis (PIGN) (p<0.001). A reduction in the frequency of MPGN (p<0.001) and MCD (p<0.001) was observed., Conclusions: This is the largest series of renal biopsy data from India; and therefore, could reflect the demographic picture of renal diseases in this country. It discusses evolving patterns over 30 yrs and highlights differences with the developed world. This report represents the basis for the future of a renal biopsy registry in India.

Intravenous immunoglobulin preparations are being used for an increasing number of indications. To minimize adverse reactions, sugar additives such as sucrose, maltose, and glycine are added to some preparations to serve as stabilizing agents. Intravenous immunoglobulin infusion induces acute renal failure (ARF) via a mechanism of osmotic nephrosis. Most reported cases are related to the use of sucrose-based intravenous immunoglobulin. Herein, we describe a patient with lupus nephritis treated with an immunoglobulin preparation containing maltose who developed ARF with histologic changes characterized by vacuolization and swelling of renal proximal tubular cells. Our case draws nephrologists' attention to the potential of maltose-based immunoglobulin in producing renal failure. Awareness and exercising caution in high-risk groups is elementary to the prevention of this condition.

Aim: A preliminary observation suggests leflunomide is effective in the treatment of cytomegalovirus (CMV) disease in renal transplant recipients. A prospective evaluation was conducted in renal transplant recipients to study the efficacy of leflunomide in the treatment of CMV disease., Patients and Methods: With prior approval and informed consent for therapy and follow-up, 17 consecutive consenting renal transplant recipients with proven CMV disease were treated with leflunomide. CMV disease was defined as a clinical syndrome of fever and/or symptoms of organ involvement, leukopenia, and a positive nested CMV quantitative PCR test at 0.001 microg/5 microL template input, with or without histologic evidence of tissue invasion. Leflunomide metabolite concentrations (A77 1726) were monitored., Results: Of the 17 patients, 14 patients were treated for 6 months for CMV disease the first time; the remaining 3 received leflunomide treatment for relapse after ganciclovir treatment, for a year. Seven patients had fever with viremia and no organ involvement, nine had viremia with involvement of gastrointestinal tract, and one had fever with CMV inclusions in the allograft, with no demonstrable viremia. The three patients with relapse treated with leflunomide responded. Overall, 15 patients (88%) clinically responded to leflunomide therapy and with viral clearance from blood and healing of involved organs. The cost of therapy with intravenous ganciclovir (Cymevene, Roche) for 2 weeks was US 721 dollars while that of leflunomide (Cleft, Cipla Ltd) for 6 months was US 64 dollars., Conclusion: Leflunomide treatment for CMV disease in renal transplant recipients is effective, simple, and economical.

Background: IgA nephropathy (IgAN) is not well characterized in India. This retrospective study of 478 patients with IgAN was performed to clarify the presenting features, prognostic factors and the renal survival rates of the disease., Methods: Three hundred and forty-seven patients who had been followed on average for 27 months after diagnosis were divided into two groups based on renal function at diagnosis. In group 1 (229 patients), the creatinine clearance estimated by the Modification of Diet in Renal Disease formula was <85 mL/min and in group 2 (118 patients) it was >/=85 mL/min., Results: The predominant modes of presentation were nephrotic syndrome, hypertension and renal failure. Twenty-nine percent of patients had more than a 20% decline in renal function at the last follow up. Multivariate analyses with stepwise logistic regression identified hypertension (odds ratio (OR) 3.5), nephrotic range proteinuria (OR 3.4) and sclerosed glomeruli on biopsy (OR 4.1) to be independently associated with progression in group 1 and hypertension (OR 2.3) in group 2. Seventeen percent of patients progressed to end-stage renal disease (ESRD). Using multivariate analysis by the Cox model, four risk factors for developing ESRD were identified: hypertension (hazard ratio (HR) 3.1); nephrotic proteinuria (HR 1.9); interstitial fibrosis (HR 2.5); and sclerosed glomeruli (HR 1.8). The renal survival rates at 1, 5 and 10 years were 84, 55 and 33%, respectively, with a median renal survival of 61 months from the time of biopsy., Conclusion: The relatively rapid rate of progression of IgAN in India is suggestive towards a 'malignant' nature of the disease in this country.

Despite significant improvements in medical care, acute renal failure (ARF) remains a high risk for mortality. It is important to be able to predict the outcome in these patients in view of the emotional and ethical needs of the patients and to address questions of efficiency and quality of care. We analyzed the risk factors predicting mortality prospectively in a group of 265 patients using univariate and multiple logistic regression analysis. A prognostic model was evolved that included 10 variables. The model showed good discrimination [(receiver operating characteristic (ROC) area=0.91) and correctly classified 88.30% of patients. The variables significantly associated with mortality were coma odds ratio (OR)=9.8], oliguria (OR=4.9), jaundice (OR=3.7), hypotension (OR=3.1), assisted ventilation (OR=2.3), hospital acquired ARF (OR=2.3), sepsis (OR=2.2), and hypoalbuminemia (OR=1.7). Age and male gender were included in the model as they are clinically important. The score was validated in the same sample by boot strapping. It was also validated in a prospective sample of 194 patients. The model was calibrated by the Hosmer-Lemeshow goodness-of-fit test. It was compared with two generic illness scores and one specific ARF score and was found to be superior to them. The model was verified in different subgroups of ARF like hospital acquired, community acquired, intensive care settings, nonintensive care settings, due to sepsis, due to nonsepsis etiologies, and showed good predictability and discrimination.

Objective: To present the first documented case of human T-lymphotropic virus type I (HTLV-I) associated myelopathy/tropical spastic paraparesis in the Australian population., Clinical Features: A 31-year-old Aboriginal man with an 18-month history of progressive weakness of the legs was found to have an upper motor neurone weakness of all limbs associated with sphincteric disturbance and impotence. HTLV-I antibodies were detected in his serum and no other cause for the patient's myelopathy could be found., Intervention and Outcome: He was counselled regarding HTLV-I associated myelopathy/tropical spastic paraparesis., Conclusion: This is the first description of HTLV-I associated myelopathy/tropical spastic paraparesis in an Australian. In cases of spinal cord disorder without evidence of compression we recommend serological testing for HTLV-I, especially in Aboriginal patients. Additionally, testing of blood donors for this retrovirus needs consideration.

Fifty-eight previously untreated adults with minimal-change nephrotic syndrome (MCNS), who had a mean follow-up period of 35.8 months, were studied with regard to their response to alternate-day steroid therapy. The nephrotic syndrome in 54 patients (93%) remitted by 12 weeks and patients continued to be in remission at 16 weeks. Of the 54 patients, 8 (14.8%) had frequent relapses and 9 (16.6%) had infrequent relapses. No serious complications as a result of steroid therapy were encountered.

Forty-six patients from 23 Indian families with hereditary chronic nephritis (HCN) with or without Alport's syndrome are presented. The occurrence of this disease in diverse Indian races, communities and castes is now documented. Clinical and laboratory findings in these patients are similar to those reported from temperate regions.

Infections were a major cause of death in 84% of 38 autopsied renal allograft recipients in a south Indian hospital. Pyogenic bacteria and fungi were the most common etiological agents encountered, being present in 50 and 47% of cases, respectively. Tuberculosis and hepatitis B virus infection were more prevalent and Pneumocystis carinii and cytomegalovirus disease rarer than in comparable series from non-tropical countries. 1 case each of amoebiasis, strongyloidiasis and filariasis were the parasitic infections encountered.

We studied the clinical profile of 296 non-insulin-dependent diabetic (NIDDM) patients with nephropathy and renal failure. Male preponderance was striking in this group and the age of onset of diabetes was between 30 and 50 years in 75%. Retinopathy was present in 86% with proliferative changes in 20% and coronary artery disease was evident in 40% of the patients. The incidence of retinopathy and coronary artery disease was significantly higher in this group than in a group of non-insulin-dependent diabetics without nephropathy (86% vs. 18.5%; 40% vs. 30% respectively, P less than 0.01). It is our observation that patients with NIDDM developing nephropathy and renal failure have had an early onset of disease and are significantly more often male. There is also a greater incidence of elevated blood pressure, coronary artery disease and retinopathy in this group.

A bilateral nasal phaeohyphomycotic infection caused by Bipolaris hawaiiensis in an immunocompromised woman from India is described. Repeated direct microscopic examinations of the nasal scrapings revealed the presence of septate, branched, pigmented hyphal fragments intermingled with cells that divided internally by one transverse septum and a few cells that were chestnut brown dividing internally by septa in different planes to become muriform. Cultures of the scrapings yielded B. hawaiiensis. Local excision of the crusted lesion followed by application of 0.03% nystatin solution four times a day for 3 weeks cured the infection.

A review of 85 patients aged 60 years or more, treated in a southern Indian hospital for conditions requiring renal biopsy, showed that diffuse poliferative glomerulonephritis was the most frequent diagnosis, being present in 24 cases of whom 11 had elevated serum streptococcal antibody titres. Infections were also important in 2 patients with amyloidosis secondary to tuberculosis, in 3 patients with acute tubular necrosis following infectious gastroenteritis and in a patient with acute pyaemic interstitial nephritis with septicaemia. Drugs including indigenous medicines were the other important cause of renal disease, being implicated in 11 cases.

Nephrotic syndrome was the commonest clinical presentation among 2827 consecutive adult Indian patients from whom adequate kidney biopsies were obtained for suspected renal disease. In 83 per cent of cases the nephrotic syndrome was due to minimal change disease, focal segmental glomerulosclerosis, mesangiocapillary glomerulonephritis, membranous usually secondary to tuberculosis or leprosy, was present in only 34 patients. Acute nephritis, the next most frequent clinical presentation, was due to diffuse endocapillary proliferative, crescentic or mesangial proliferative glomerulonephritis in 88 per cent of cases, almost half of whom had elevated serum streptococcal antibody titres. Eosinophilia showed a highly significant association with diffuse endocapillary proliferative and mesangiocapillary glomerulonephritis. Idiopathic IgA nephropathy was present in only 10, and antiglomerular basement membrane antibody disease in only one, of the 238 patients whose biopsies were studied by immunofluorescence. Complications of pregnancy accounted for 70 per cent of cases of cortical necrosis. Acute gastroenteritis, septicaemia, abortions, snake bite and allopathic and indigenous medicines were important causes of acute tubular necrosis.

In a study of 656 urine specimens from 53 consecutive recipients of live related donor renal allografts we found an excellent correlation between the protein content of 24-h urines and protein/creatinine ratio (Up/Ucr) in overnight urine samples. Using this ratio, we evaluated proteinuria up to 180 days after renal transplantation (overnight urine samples analysed, n = 2745). Heavy proteinuria in the immediate post-operative period had no prognostic significance. Eighty-nine percent of all clinically observed acute rejection episodes were accompanied by an increase over baseline of Up/Ucr; in 56.5% of these episodes elevation of Up/Ucr preceded that of serum creatinine. However, as a marker of rejection the usefulness of this parameter was limited owing to large number of false positive elevations. In 50 recipients whose grafts survived for more than 3 mth, proteinuria was graded into minimal, moderate and heavy. Renal function at the end of six months was good in all patients who exhibited proteinuria with Up/Ucr less than 100 mg/mmol creatinine. Persistent proteinuria with Up/Ucr above 100 mg/mmol preceded significant deterioration of graft function. Therefore, a protein-creatinine ratio of 100 mg/mmol can be considered as an apparent cut-off to differentiate stable from deteriorating graft function in long term evaluation of transplant recipients.

A case is reported of Bancroftian filariasis and acute immune complex glomerulonephritis in a 44-year-old man. Renal biopsy showed microfilariae and large numbers of eosinophils in the glomeruli (eosinophilic glomerulonephritis). The absence of other aetiological factors suggests that the glomerulonephritis may have been of filarial origin.

A retrospective study of children admitted to a south Indian hospital during an 11 year period showed that 70% of the renal diseases encountered in children in this region are of types which have a good prognosis. Post-streptococcal glomerulonephritis was the most common. The relative prevalence of steroid-sensitive nephrotic syndrome and different histological types of idiopathic nephrotic syndrome was similar to that in developed Western countries. Haemolytic-uraemic syndrome complicating bacillary dysentery was the most common cause of acute renal failure.

The clinical pattern of nephropathy was studied in 498 diabetic patients who were hospitalized during the period 1980-1985 at the Christian Medical College Hospital, Vellore, India. The diagnosis of nephropathy was confirmed in the presence of persistent proteinuria of 500 mg or more in any 24 hour urine sample in the absence of urinary infection and congestive failure. Only four patients had Type I diabetes, all the rest being non-insulin-dependent (Type II). There was significant male preponderance, and the largest number of patients were in the fifth and sixth decades. The age of onset in Type II diabetics was between 30 to 50 years in 74%; 55% of the patients were known to have diabetes for less than 10 years, and in only 6% was the duration greater than 20 years. The degree of renal failure and proteinuria showed a variable pattern in relation to the duration of diabetes. Arterial hypertension was present in 80% of the patients and coronary artery disease in 33.5%, while cerebrovascular disease and peripheral vascular disease were evident in 7.4 and 4.8%, respectively. Fundoscopic examination showed evidence of retinopathy in 278 patients (53%), with proliferative changes in 17%. Clinical evidence of retinopathy was absent in 110 patients (22%), and in the rest the results of fundus examination was not documented; thus, the incidence of clinical retinopathy in this review was 72% (278/388). It is concluded that contrary to what has been observed in Type I diabetes, the progression of nephropathy in Type II bears no relationship to the duration of disease, nor is retinopathy a constant feature.