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One way to prevent chronic renal failure (CRF) is to institute preventive measures against renal diseases in the general population. Patients with hereditary kidney diseases should have genetic counselling. Certain infections affecting or causing kidney diseases can be eradicated. People should be cautious in the use of analgesics and non-steroidal anti-inflammatory agents. Exposure to hydrocarbons, heavy metals and toxic gases should be avoided. Proper management of diabetes mellitus, gout, renal stones and hypertension can prevent renal damage. In patients with established renal disease, the following factors if treated or modified can prevent or ameliorate renal injury: glomerular hypertension, cell mediated proliferation, lipid induced proliferation, coagulation and thrombosis. Pregnancy in patients with renal disease should be well managed and termination advised if necessary. Reversible causes of renal failure as well as acute reversible elements can be removed or treated. Acute renal failure due to toxins can be avoided, although prevention requires awareness of association with renal failure. Prevention too depends on early detection of nephrotoxic injury like: greater awareness of hazards of environmental toxins, careful monitoring of dosage of nephrotoxic drugs and when possible, total avoidance of nephrotoxins should be the rule. Finally, in patients with glomerular disease, prevention or amelioration of glomerular damage with pharmacological agents have been achieved in some instances.

In Asian countries, it is more difficult to obtain cadaver kidneys for renal transplantation because of certain socio-cultural beliefs and customs. The issues affecting living related kidney donation are more social than cultural. This is due to the web of family pressures and personal conflicts for both donor and recipient surrounding the donation. Important misconceptions and fears are: fear of death, the belief that removal of organ violates sanctity of decreased, concern about being cut up after death, desire to be buried whole, dislike of idea of kidneys inside another person, wrong concept of brain death, and the idea of donation being against religious conviction. In Singapore, with the introduction of the Human Organ Transplant Act (HOTA) in 1988, the number of cadaveric transplants have increased, including those from the Medical Therapy Act (MTA). HOTA and education have played pivotal roles in bringing about an increased yield of cadaveric kidneys. With the availability of living unrelated donor (LUD) transplants in India, our living related donor (LRD) transplant programme has suffered, because patients would rather buy a kidney from overseas than get a relative to donate one. Patients are also going to China for overseas cadaveric transplants where the kidneys come from executed convicts. People in countries like Hong Kong, Japan and the Philippines share the same Asian tradition of not parting with their organs after death. Muslim countries like Malaysia require the deceased to have earlier pledged his kidneys for donation prior to death before they can be harvested for transplantation at death.

The prevalence of antibodies to the hepatitis C virus (anti-HCV) in Singapore was assessed using a recombinant-based enzyme linked immunoassay system. 1004 serum samples were obtained from normal subjects (463), hemodialysis patients (112), hepatitis B virus (HBV) carriers (188), patients with hepatocellular carcinoma (HCC) (58) and patients with non-hepatitis B virus related liver diseases (183). Anti-HCV was found to be positive in 1.7% of healthy subjects, and in 20% of patients on regular hemodialysis. Three percent of HBV carriers were positive for anti-HCV. Twelve percent of patients with acute hepatitis with no known causes and 20% patients with chronic hepatitis with no known causes were positive for anti-HCV. Among patients with cirrhosis for which no known causes were found 33% were positive for anti-HCV. Thirty six percent of patients with HCC not associated with the presence of HBsAg were positive of anti-HCV. None of the patients with known causes of liver disease were positive for anti-HCV.

This study is a 5-year post trial assessment of patients with IgA nephritis who entered a 3-year prospective controlled trial of cyclophosphamide, dipyridamole (D) and low-dose warfarin (W). Patients entered the trial from 1979 to 1981 and the trial ended in 1984 with those in the treatment group having more stable renal function and less proteinuria compared to the control group. Present reassessment of the patients in 1989 showed no difference in the renal function between those in the treatment group (n = 27) and the control group (n = 21). 6 patients in the treatment group and 7 in the control group were in ESRF. At the conclusion of the trial in 1984, among the 27 patients in the original treatment group, 13 patients elected to continue with D + W while the other 14 patients chose to cease therapy and therefore served as the new control group. 5 years later, renal function in the new treatment group (n = 13) was significantly stable compared to the new control group (n = 14), (serum creatinine 1.4 +/- 0.7 versus 4.4 +/- 3.2 mg/dl, p less than 0.01). Furthermore, all the 6 patients with ESRF in the original treatment group of 27 patients were from the new control group (n = 14) where treatment with D + W had been ceased. None of the patients still on D + W are in ESRF.

Of sixty patients with IgA nephritis, none had CRF at first examination, 13 developed CRF with creatinine above 1.6 mg/dl within 6 years. Among these patients who had analysis of proteinuria by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), 31 patients had middle molecular weight (MMW) proteinuria alone (pattern 1), 10 had MMW and Low MW (LMW) or tubular proteinuria (pattern 2), 10 had high MW (HMW) and MMW proteinuria (Pattern 3) and 9 had HMW, MMW and LMW proteinuria (Pattern 4). At the end of a follow up period of 6 years (1983-1989) patients with mixed proteinuria had a higher incidence of chronic renal failure (CRF), 11/29 (38%) compared to those with pattern 1 proteinuria, 2/31 (6%) (chi 2 = 8.7, p less than 0.005). Based on the glomerular selectivity index (GSI), 19 patients had nonselective proteinuria but they did not have a higher incidence of CRF. By the selectivity index (SI), 18 patients had nonselective proteinuria and they showed a significantly higher incidence of CRF. Compared to the 41 patients who did not have LMW proteinuria, 19 patients with LMW proteinuria had more severe proteinuria. After a follow-up period of 6 years, patients with LMW proteinuria had a higher incidence of CRF (10% versus 47%, p less than 0.001). The presence of LMW proteinuria indicates a less favourable outcome and the pattern of proteinuria as assessed by the SDS-PAGE appears to be a better prognostic index in IgA nephritis than the SI and the GSI.

Cyclosporine (CsA) is a potent immunosuppressive agent which has dramatically improved graft and patient survivals in clinical solid organ transplantation. However, CsA nephrotoxicity (NTX) is the most frequent and serious side effect of CsA therapy and occurs in a significant proportion of patients. The clinical presentation of NTX is that of reduced creatinine clearance, elevation of serum creatinine and a disproportionate rise in blood urea. The clinical picture occurs as three syndromes, namely acute, subacute and chronic CsA NTX. Regardless of the clinical syndrome, the pathoaetiology of NTX is related to decline in renal blood flow and increase in renal vascular resistance probably due to CsA induced changes in renal haemodynamics. Unfortunately, the dose that yields an optimal therapeutic index, namely maximal efficacy with minimal toxicity has yet to be defined. Optimal dosing is confounded by not only inter and intraindividual variabilities in drug absorption, distribution and metabolism, but also by the lack of a clear relationship between drug efficacy and trough CsA level monitoring. This paper describes the pharmacokinetics and nephrotoxicity of CsA and evaluates various strategies to overcome this toxicity.

The chronic haemodialysis programme of the Singapore General Hospital started in 1968 as a hospital-based fully nurse-assisted programme. This has since expanded to include Self Dialysis and Home Dialysis programmes. Data of 425 patients who entered the dialysis programmes was analysed retrospectively. The major cause of end stage renal failure was chronic glomerulonephritis (52%). Almost half of the patients in the haemodialysis programme were patients on self-dialysis (49%). There were 157 withdrawals and 116 deaths. Survival has improved tremendously with the use of treated water for dialysis from 1981. The 5 year survival in an earlier group of patients dialysed with untreated water was 48% compared with 81% in a late group dialysed with treated water (p less than 0.001). The pattern of complications has also changed with a lower incidence of dialysis osteomalacia, hypertension, hepatitis and eradication of dialysis dementia.

Forty-eight patients with acute renal failure (ARF) who were referred to the Department of Renal Medicine, Singapore General Hospital for acute dialysis between August 1985 and August 1989 were studied retrospectively to identify risk factors associated with ARF that serve as prognostic indicators. There was no difference in the mean age of survivors and non-survivors (49.5 +/- 17.5 years vs 53.5 +/- 18 years, p greater than 0.05). The overall mortality rate was 52%. ARF as a result of surgical complication had a higher mortality rate in comparison to ARF from medical complications (66% vs 50%, p greater than 0.05). Septicaemia was the most common cause of ARF requiring dialysis. Hepatobiliary sepsis was the most frequent cause of septicaemia. Pre-dialysis serum urea and creatinine levels, and the number of dialysis treatments did not affect the outcome. Poor prognostic indicators included oliguria or anuria, fluid overload and coma. Patients tended to have a worse outcome if they had more than three risk factors taken from the following list:-decreased renal perfusion, assisted ventilation, coma, gastrointestinal dysfunction, recent surgery, sepsis, congestive heart failure, hepatobiliary dysfunction, malignancy, diabetes mellitus, chronic renal insufficiency and poor nutritional status. Early referral of patients with septicaemia due in particular to hepatobiliary infection may improve the prognosis.

Immunosuppression with Cyclosporin A has resulted in dramatic improvements in the results of cadaveric kidney transplantation in Singapore. However, its major limitation is its nephrotoxicity which can appear in various forms after transplantation including a delay in graft function and chronic renal dysfunction. The clinical course of two patients with initial function but delayed onset of acute functional Cyclosporine nephrotoxicity are described. Recovery was documented in both cases with reduction of Cyclosporine dosage. A decline in renal blood flow and increase in renal vascular resistance is likely to have played a role in the pathogenesis of the acute functional nephrotoxicity. Cyclosporine induced imbalance in Prostaglandin synthesis within the kidney has been implicated.

Thirty-two patients with end stage renal failure who were on haemodialysis and who had no previous exposure to hepatitis B virus were given four intramuscular injections of 40 micrograms (twice the recommended dose) recombinant DNA hepatitis B vaccine (Engerix B, Smith Kline Biologicals) at 0, 1, 2 and 6 months to determine the immunogenicity of this increased vaccine dose. The ages of these patients ranged from 23-54 years with a mean age of 40 years. There were 11 males and 21 females. Three patients underwent renal transplantation during the course of the study and were assessed separately. Antibody levels above 10 IU/L were noticed in 83% of the remaining 29 patients two months after the final dose with an anti-HBs geometric mean titre (GMT) of 2551 IU/L. The antibody response was 82% four months later although the GMT has fallen to 664 IU/L. Renal transplantation did not appear to affect the anti-HBs response to the above vaccination regime. None of the volunteers developed hepatitis B during the study. Our results were much better than results obtained in studies using twice the recommended doses given three times.

A patient with lymphatic filariasis, developing the nephrotic syndrome is reported. Renal biopsy showed a diffuse mesangial proliferative glomerulonephritis with C3 deposition in the glomeruli. Glomerulonephritis associated with filariasis has been reported previously, however definite identification of filarial antigen in glomerular deposits or of specific antibodies in kidney eluates is still awaiting.

Circulating platelet aggregate ratios (CPAR) and plasma beta-thromboglobulin (B-TG) concentrations were determined in 53 patients with chronic progressive glomerulonephritis [mesangiocapillary glomerulonephritis (15) and focal and segmental hyalinosis and sclerosis (38)] and compared with those from both normal subjects and patients with no evidence of renal disease. The mean B-TG concentration was higher in patient controls [32.6 +/- 6.2 ng/ml (SEM)] than in normal subjects [19.0 +/- 2.0 ng/ml (SEM)] but this did not reach significance (P < 0.10 > 0.05). Nephritic patients had markedly elevated levels [49.8 +/- 4.0 ng/ml (SEM)], but B-TG was significantly correlated with renal impairment. Elevated B-TG levels in patients with nephritis may thus reflect renal impairment or ill-health. The mean CPAR of the nephritic patients [0.75 +/- 0.02 (SEM)] was lower than that of both normal [0.86 +/- 0.03 (SEM), P < 0.001] and patient controls [0.87 +/- 0.02 (SEM), P < 0.001]. CPAR was not correlated with renal function or platelet concentration. Low CPAR in nephritic subjects provides further evidence for in-vivo activation of platelets in patients with glomerulonephritis.

Suppressor cell function was assessed in 13 patients with chronic renal failure not on dialysis, 10 patients on regular hemodialysis and 11 renal transplant patients by means of the Concanavalin A inducible Suppressor Cell Assay. The mean Suppression Index (S.I.) in the undialysed patients (0.76 +/- 0.39) and those of the dialysed patients (0.72 +/- 0.18) were not significantly different from the 25 healthy controls (0.68 +/- 0.22). However the S.I. in the renal transplant patients (1.11 +/- 0.41) was significantly different from the normal controls as well as the undialysed and dialysed patients. Although there was no correlation between S.I. and age, post transplant follow up period, serum creatinine concentration, prednisolone or azathioprine dosage it is likely that the cause of the impaired suppressor cell function was due to the immunosuppressive agents used.

We examined the occurrence of crystals and casts in the urine of healthy subjects after administration of triamterene and the site of crystal formation in experimental animals. Twenty out of twenty healthy subjects had abundant triamterene crystals and casts in acid urine after receiving a single 100 mg dose. Casts were present in the urine from 2-11 hours after administration of the diuretic. Cast formation occurred in acidic urine and was prevented by alkalinization of the urine with potassium citrate. Animal studies showed that crystallization and cast formation occurred in the medullary and papillary collecting ducts of the rat kidney. These findings provide a possible explanation for the reported nephrotoxicity of triamterene, particularly when given to patients who are receiving non-steroidal anti-inflammatory agents.

This study examined the frequency of anti-vascular endothelial cell (VEC) antibodies (Ab) in 72 patients with IgA nephropathy (IgAN), and their possible relationship to clinical and histological parameters of the disease. An enzyme immunoassay was developed to measure the binding of sera to endothelial cells grown to a confluent monolayer. Thirty-two percent of IgAN patients had serum anti-VEC activity as compared to 4% of controls (P = 0.004) and 9% of patients with other primary glomerulonephritis (P = 0.017). This was shown to be due to anti-HLA class I Abs in 6 of the 23 IgAN patients, and in the 1 control positive for anti-VEC activity. Hence 17 IgAN patients had anti-VEC Abs, predominantly of the IgA subclass. Stimulation of the endothelial cells with interferon-gamma and interleukin 1 did not increase the binding of these Abs. There was no correlation with circulating immune complex (IC) levels, and removal of ICs in positive sera by ultracentrifugation did not decrease anti-VEC binding. Significant correlations were found between anti-VEC Abs and proteinuria greater than 1 g/day (P = 0.044), as well as IgA anti-VEC Abs and C3 or IgA deposition in renal arterioles (P = 0.048). These IgA Abs may be an important marker of pathogenetic activity in IgAN.

The clinical and histological features of 151 patient with IgA nephritis were analyzed to determine the prognostic features of the disease. The mean duration of follow up examinations was 50 +/- 34 months (range 6 to 168 months). The majority of the patients were young males and showed no signs of IgA nephritis. The disease was detected by routine screening before induction into national service. The plot of the reciprocals of serum creatinine against time in the patients with progressive disease showed that the patients ran two different courses when they developed renal impairment; one was a slow progressive course over an average of 7.7 years before reaching end stage renal failure (ESRF), while the other was a more rapid decline to ESRF within an average of 3.3 years in which severe uncontrolled hypertension seemed to be the major adverse factor. Hypertension was present in 23% of patients. Nine percent had renal impairment at the end of the follow up period while 5% progressed to ESRF. The cumulative renal survival was 91% after 6 years with no further development of renal failure up to 14 years. Unfavorable long term prognostic indices were proteinuria of more than 2 gm, hypertension and presence of crescents on renal biopsy.

Using the method of concanavalin A (Con a) inducible suppressor activity the peripheral mononuclear cells (PMC) of 17 patients with Mesangial IgA nephritis, 13 patients with idiopathic mesangial proliferative glomerulonephritis but with no IgA deposits on immunofluorescence (Non-IgA nephritis) and 18 healthy subjects were studied. DNA synthesis was measured by incorporation of 3H Thymidine. The mean suppression index (S.I.) of 0.94 +/- 0.08 (SEM) in the IgA nephritic patients was significantly different from that of the non-IgA nephritic patients (0.67 +/- 0.05) (P less than 0.01) as well as the group of normal healthy controls (0.64 +/- 0.05) (P less than 0.0025). The data show that patients with IgA nephritis have abnormal suppressor cell function and suggest an autoimmune basis in the pathogenesis of IgA nephritis.

The glomerular lesions of 90 patients with asymptomatic glomerulonephritis and proteinuria of more than 1.0 gm per day were compared with 8.3 similar patients with less than 1.0 gm proteinuria. 68% of those patients with more than Igm proteinuria had glomerular sclerosis compared to 19% of those with less than Igm proteinuria (p less than 0.001). Immunofluorescence studies revealed that 77% of patients studied had IgA deposits in the mesangial region. There was no correlation between the degree of microscopic haematuria and the severity of glomerular lesions. Patients with more than 1 gm proteinuria also had significantly higher incidence of granular casts (p less than 0.001) and the presence of casts was also significantly associated with the finding of glomerular sclerosis (p 0.005). The data suggest that 1 gm proteinuria is a useful predictive index of glomerular sclerosis in patients with asymptomatic urinary abnormalities.

Plasma antithrombin III (AT III) levels in hemodialysis patients, low prior to dialysis, improved after dialysis (p less than 0.01). The platelet counts before and after dialysis, did not change significantly. In peritoneal dialysis patients the AT III levels, which were normal before dialysis, increased significantly after dialysis (p less than 0.01). The platelet counts before and after peritoneal dialysis also improved (p less than 0.005). No correlation was found between AT III levels and platelet counts. Although platelet damage has a contributory role in increasing AT III levels during hemodialysis, the data on peritoneal dialysis suggest that there may be other factors affecting platelets and AT III during dialysis.

Among 151 patients with IgA nephritis, 18/151 (12%) had hypertension at presentation and 50/151 (33%) were hypertensive after an interval of 65 +/- 40 (Mean +/- SD) months. Hypertensive patients (n = 50) had a higher incidence of glomerulosclerosis, medial hypertrophy of blood vessels, tubular atrophy, poorly selective proteinuria and extension of immunodeposits to peripheral capillary walls compared to normotensive patients (n = 101). Chronic renal failure occurred more commonly among hypertensives compared to normotensive patients (42%) versus 14%. However, the time taken for patients to reach renal impairment or end stage renal failure was not significantly different. The cumulative renal survival for the hypertensive group was 78% after 8 years compared to 91% in the normotensive group (p less than 0.05). In the second part of the study, patients who were hypertensive at presentation (n = 18) were compared with those who developed hypertension on follow up (n = 32). Apart from a shorter duration of follow up for patients with hypertension and a higher incidence of glomerulosclerosis, there were no significant differences in their clinical presentation, laboratory indices or other histological parameters. The incidence of chronic renal failure and the time taken to reach end stage renal failure were not different. Uncontrolled hypertension was an important cause for rapid deterioration to end stage renal failure within 3 years, compared to 8 years when hypertension was controlled.

Plasma beta-thromboglobulin (beta-TG) concentration were determined in 28 patients with mesangial IgA nephritis (17 with focal glomerular sclerosis and 11 without any glomerular sclerosis) and compared with those from 52 normal subjects and 24 patients controls with no evidence of renal disease. The mean beta-TG concentration in the patients with IgA nephritis [159 +/- 63 ng/ml (SD)] significantly different from the patients controls [32 +/- 25 ng/ml (SD)] (p less than 0.001) as well as the group of normal subjects [23 +/- 17 ng/ml (SD)] (p less than 0.001). In another group of 12 patients with diffuse mesangial proliferative glomerulonephritis with no IgA deposits (non IgA nephritis) the mean beta-TG concentration [126 +/- 86 ng/ml (SD)] though different from that of the normal as well as patient controls (p less than 0.001) was not significantly different from the IgA nephritis patients. The elevated beta-TG levels in the nephritic patients showed no correlation with serum creatinine, creatinine clearance or proteinuria but was significantly correlated with the degree of glomerular sclerosis (r = 0.44) (p less than 0.05). In vivo activation of the platelets is suggested by these findings of elevated beta-TG in patients with diffuse proliferative mesangial glomerulonephritis (IgA and non IgA).

Paraquat poisoning has become a significant clinical problem since the early 1960s. Its high mortality has posed a major challenge to clinicians treating these patients. Two patients who survived and one who did not are reported. The management of these patients and the possible factors affecting their outcome are discussed.

Plasma Antithrombin III (A T III) was measured in 97 patients with IgA nephritis, 30 patients with non IgA idiopathic mesangial proliferative glomerulonephritis and 40 healthy subjects. The mean plasma A T III levels in the patients with IgA nephritis (105 +/- 10%) was significantly higher than those of normal controls (96 +/- 5%) (p less than 0.0005). The mean plasma A T III levels in the patients with non IgA nephritis (101 +/- 10%) was not different from those of the normal controls or the patients with IgA nephritis. A T III levels were significantly correlated with proteinuria (p less than 0.0001), segmental sclerosis (p less than 0.001), crescents (p less than 0.01), medial hypertrophy (p less than 0.001) and intensity of IgA staining on IMF (p less than 0.02). Patients with IgA nephritis with raised A T III levels had significantly more proteinuria (p less than 0.003), more segmental sclerosis (p less than 0.007) as well as a greater intensity of IgA staining on IMF (p less than 0.02) when compared to patients with normal A T III levels. The data suggest that raised plasma A T III levels may serve as a prognostic marker in IgA nephritis.

Antithrombin III (AT III) is increased in situations where there is increased platelet turnover. Plasma AT III levels measured in 39 renal transplant recipients were significantly higher than in 20 healthy subjects (p less than 0.001) and 20 patient controls (p less than 0.025). AT III levels were significantly correlated with the patients' platelet counts (r = 0.4, p less than 0.02). Transplant patients with less than 1 year follow up had significantly higher AT III levels than patients with more than 1 year follow up (p less than 0.01). All 5 patients with transplant rejection in the study had elevated plasma AT III levels. The data suggest that elevation of plasma AT III may be related to graft rejection.

The renal biopsies of 100 patients presenting with the Nephrotic Syndrome were analysed. Eighty-seven percent were due to primary glomerulonephritis and the other 13% due to secondary glomerulonephritis of which Systemic Lupus Erythematosus was the commonest. Diffuse mesangial proliferative glomerulonephritis (DPGN) formed the largest group (60%). Minimal lesion occurred in 15% of patients and only 5% had Membranous Glomerulonephritis. 63% of patients with DPGN had negative staining on immunofluorescence. Even though Mesangial IgA Nephritis is prevalent in Singapore, it accounted for only 4% of glomerulonephritis causing the Nephrotic Syndrome.

Alimentary antigenic challenge has been postulated to have a role in the genesis of IgA circulating immune complexes (CIC), resulting in mesangial IgA disease. In this study, we examined the relationship between bovine serum albumin (BSA) and IgA CIC in patients with IgA nephropathy. Of the 47 patients studied, elevated IgA CIC levels were found in 32% by the F(ab')2 anti-C3 and Raji cell enzyme immunoassays (EIA). Elevated IgA anti-BSA antibody levels were found in 9 patients, and there was a positive correlation between these levels and IgA CIC as measured in the Raji cell EIA (R = 0.60, P less than 0.001). In 4 patients with elevation of both IgA CIC and IgA anti-BSA antibody levels, solubilization experiments were done to demonstrate the presence of BSA antigen in the IgA CIC. Using the Raji cell EIA, the IgA CIC levels decreased significantly after preincubating the sera with serial concentrations of excess BSA. No corresponding effect was seen with human serum albumin used as control. Hence, BSA may be the antigenic stimulus in the formation of IgA CIC in selected patients with IgA nephropathy. The pathogenic capacity of these IgA-BSA CIC remains to be determined.

This study measured plasma beta 2-microglobulin (beta 2-m) in patients with mesangial IgA nephritis. Plasma beta 2-m was measured in 51 patients with IgA mesangial nephritis and in 50 normal controls using a Phadebas beta 2-m RIA kit available from Pharmacia Diagnostics (Uppsala, Sweden). The mean plasma beta 2-m in IgA nephritic patients (1.92 +/- 0.67 mg/l) was significantly different from that of healthy controls (1.33 +/- 0.41 mg/l; p less than 0.001). The mean plasma beta 2-m in non-IgA nephritic patients (1.83 +/- 0.73 mg/l) was also significantly different (p less than 0.001). Patients with IgA nephritis with glomerular sclerosis (n = 33) had significantly higher levels of beta 2-m (2.02 +/- 0.70 mg/l) than IgA nephritic patients without glomerular sclerosis (n = 18, 1.72 +/- 0.65 mg/l; p less than 0.025). In the group with IgA nephritis and glomerulosclerosis, raised beta 2-m levels were correlated with the severity of proteinuria (r = 0.41) (p less than 0.02) as well as the intensity of IgA staining on immunofluorescence (r = 0.34; p less than 0.05). Elevated beta 2-m levels in IgA nephritis may serve as a useful prognostic marker.

Among 98 patients with IgA nephritis who had protein selectivity studies performed, 54% had nonselective proteinuria and the remaining 46% had selective proteinuria. Patients with nonselective proteinuria had a higher incidence of glomerulosclerosis. At the end of a 4-year follow-up period, patients with nonselective proteinuria had lower creatinine clearance, higher incidence of hypertension and chronic renal failure when compared to patients with selective proteinuria. Six out of eleven patients (55%) in the study who had the nephrotic syndrome had selective proteinuria. Among these 6 patients, 1 had spontaneous remission and 5 responded to steroid or cyclophosphamide therapy. The remaining 5 patients with nonselective proteinuria did not respond to therapy. In the patients who had selectivity studies repeated, the data showed that the selectivity index (SI) can fluctuate depending on the clinical course of the patients. SI can therefore be used to monitor the progress of patients on long-term follow-up. Protein selectivity appears to be a useful prognostic index in IgA nephritis. For patients with the nephrotic syndrome it may serve as a guide to therapy.

The pattern of glomerulonephritis (GN) consisting of 1057 renal biopsies is presented. Primary GN accounted for 91% and secondary GN 9% of which the commonest is lupus nephritis. Asymptomatic haematuria and proteinuria was the commonest mode of presentation (41%), gross haematuria 9%, nephrotic syndrome 29% while 5.5% presented with renal impairment and 4.3% with hypertension. Mesangial proliferative GN is the commonest histopathological lesion forming 66% of all primary GN. Minimal Lesion, Focal Global Sclerosis and Focal Segmental Glomerulosclerosis accounted for 7% each. Membranous GN was uncommon (3%) while Mesangiocapillary GN, Diffuse Endocapillary GN and Crescentic GN were even rarer. If the presenting feature was asymptomatic haematuria and proteinuria the likely diagnosis was IgA nephritis, and, if nephrotic syndrome it was likely to be Idiopathic Mesangial Proliferative GN but with negative staining on immunofluorescence. The course and prognosis of the various forms of GN are next discussed. Nephrotic syndrome with Minimal Lesion has an excellent prognosis while Crescenteric GN usually carries a grim prognosis. Finally, factors affecting the progression of IgA nephritis, the commonest form of GN occurring in Singapore are examined. Patients who developed renal failure ran two different courses; one was a slowly progressive course over an average of 7.7 years before reaching end stage renal failure (ESRF), while the other was a more rapid decline to ESRF within an average of 3.3 years where severe uncontrolled hypertension seemed to be the major adverse factor. 9% had renal impairment at the end of a follow up of 50 + 1/2 - 34 months while 5% progressed to ESRF. The cumulative renal survival was 91% after 6 years with no further loss up to 14 years. Unfavourable long term prognostic indices were proteinuria of more than 2 gms, hypertension, crescents on renal biopsy, severe segmental sclerosis and medial hypertrophy of blood vessels.

The protein selectivity index was measured in 68 patients (53 males, 15 females) with proteinuria due to IgA nephropathy to determine whether it bore any relationship to other clinical and pathological features of known prognostic significance. The mean age of the patients was 25 +/- 8 years with a follow-up period of 42 +/- 35 months. Forty-six presented with asymptomatic haematuria and proteinuria, 17 with macroscopic haematuria and 5 with the nephrotic syndrome. Twenty-three (34%) patients had selective proteinuria and 45 (66%) had non-selective proteinuria. Patients with non-selective proteinuria had more glomerulosclerosis (29% +/- 20 vs. 16% +/- 20, p less than 0.02), higher serum creatinine (1.47 mg/dl +/- 0.70 vs. 1.17 mg/dl +/- 0.33, p less than 0.02), lower creatinine clearance (79 ml/min +/- 28 vs. 95 ml/min +/- 25, p less than 0.02), and higher incidence of hypertension (chi 2 = 3.84, p less than 0.05) when compared to those with selective proteinuria. The protein selectivity was measured at the end of the study. Of the 5 patients with the nephrotic syndrome, 1 had poorly selective proteinuria and failed to remit and 4 had highly selective proteinuria who either remitted spontaneously (1 patient) or with treatment (3 patients). The results suggest that patients with IgA nephropathy and poorly selective proteinuria are more likely to have other features indicating a poor prognosis such as glomerulosclerosis, renal impairment and hypertension.

The clinical features and biochemical profile of 10 patients with Renal Tubular Acidosis (RTA) were described. The commonest mode of presentation was muscular weakness due to severe hypokalaemia in 5 patients while the other 5 presented with renal colic, haematuria or passage of gravel. Nine patients had nephrocalcinosis on X-rays and one had rickets. All the patients had Type I RTA, 2 of whom presenting initially with Incomplete Type I RTA which progressed to Complete Type I RTA. Two other patients had associated features of proximal tubular involvement evidenced by hypophosphatemia, hypouricemia, hyperphosphaturia, aminoaciduria and glycosuria. Six of the 10 patients had secondary RTA: 2 associated with medullary sponge kidneys, 2 with gout, 1 with idiopathic hypercalciuria and hyperuricosuria and the remaining patient with systemic lupus erythematosus.