Glomerular lesions in asymptomatic microscopic hematuria discovered on routine medical examination.

Renal biopsies from 145 patients with asymptomatic microscopic hematuria were studied with light microscopic, electron microscopic and immunofluorescence antibody techniques. The predominant lesions were a diffuse proliferative glomerulonephritis (mesangial hypercellularity) with focal epithelial crescents and focal segment and/or global sclerosis in many of them; and a minimal lesion with increased mesangial matrix and mild mesangial hypercellularity. Focal and segmental glomerulonephritis, diffuse mesangio-capillary and membranous glomerulonephritis were less common lesions. IgA deposition with other immunoglobulins was seen in over 50% of cases, with an IgA IgG-Beta1C-globulin combination being the common lesion. IgA secretory piece and HBs antigen were not found in the glomeruli and early complement components C1q and C4 were absent. Changes in the mesangium, basement membranes of capillary loops and mesangial osmophilic deposits reflect the pathogenesis of this disease. In addition to the above 145 patients, thirty-five cases of persistent microscopic hematuria classified as symptomatic, with a past history of "acute nephritis", lumbar pain and other complaints; and 11 patients with macroscopic hematuria, painless or associated with "acute nephritis" had similar glomerular lesions. Raised ASOT levels suggest the role of an upper respiratory infection in the exacervation or precipitation of this lesion. The IgA depositon may be associated with deposition of other antibodies in a picture of chronic glomerulonephritis, post-streptococcal or otherwise. 6 of the 145 patients with asymptomatic microscopic hematuria have gone into chronic renal failure in 3.5 years.

Glomerular lesions in patients with asymptomatic persistent andorthostatic proteinuria discovered on routine medical examination.

The incidence of asymptomatic proteinuria in young healthy men entering the army service in Singapore was 0.94%; 0.56% had intermittent orthostatic proteinuria and 0.38% with persistent proteinuria. Renal biopsies from 45 cases with persistent proteinuria and 10 cases with orthostatic proteinuria were studied by light microscopy, electron microscopic and immunofluorescent antibody techniques. Three cases with orthostatic proteinuria showed a minimal lesion ('Nil'), and 7 a minimal lesion with increased centrilobular mesangial matrix and mild focal and segmental mesangial hypercellularity. Focal and segmental capillary loop changes were seen in two cases. No immunoglobulin deposits were found in orthostatic proteinuria. A raised anti-streptolysin O titer was found in 3 cases. 13.3% of cases with persistent proteinuria showed a minimal lesion ('Nil'); 66.6% a minimal lesion with increased centrilobular mesangial matrix and mild focal and segmental mesangial hypercellularity: Focal global sclerosis, focal segmental sclerosing glomerulonephritis and diffuse proliferative GN (mesangial hypercellularity) were each found in 6.7% of patients in this group. Focal and segmental changes in capillary loops were found in 30% of cases. Changes in visceral epithelium such as the appearance of cytoplasmic swelling, vesicles and dense aggregates, and areas of focal foot process fusion were common findings. Mesangial deposits of IgA were found in 34.3%, with an IgA-IgG-beta1C globulin combination in 28.6% of cases. IgM-beta1C globulin was present in 5.7% of cases with persistent proteinuria. Early complement components, C1q and C4, and IgA secretory piece were absent. A raised antistreptolysin O titer was found in 25% of cases. The changes inthe glomeruli may represent the end or healing stages of an early bout of glomerulonephritis. Changed hemodynamic responses on assuming an upright position may play a role in the loss of protein across the glomerular basement membrane in patients with orthostatic proteinuria.

Effects of triple therapy on the progression of mesangial proliferative glomerulonephritis.

Fifty-two pairs of patients with idiopathic diffuse mesangial proliferative glomerulonephritis entered a controlled 3-year prospective trial of a combination regimen of cyclophosphamide, dipyridamole and warfarin. In the treatment group proteinuria decreased significantly (p less than 0.01) and renal function remained stable, but in the control group there was no change in proteinuria and creatinine clearance (Ccr) decreased significantly (p less than 0.01). The time patients with renal impairment in the control group and those in the treatment group took to reach end stage renal failure was significantly different (6.1 years versus 8.9 years, p less than 0.02). Among the patients with IgA nephritis, those in the treatment group (n = 27) had stable renal function and a significant decrease in proteinuria (p less than 0.01) but in the control group (n = 21) there was a significant fall in Ccr (p less than 0.01) and rise in serum creatinine (p less than 0.02) with no change in proteinuria. Among 23 pairs of patients in the study who were matched for renal function and degree of glomerulosclerosis, those in the treatment group had stable renal function and decrease in proteinuria (p less than 0.01) whereas those in the control group had decreased Ccr (p less than 0.01) but no change in proteinuria.

The natural history of IgA nephritis in Singapore.

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.

Maintenance haemodialysis in Singapore.

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.

The history of dialysis in Singapore.

The last 20 years has been seen the birth of nephrology in Singapore, starting from a single machine in a side room of a ward to a fully fledged unit with a satellite centre. Renal transplantation and hemodialysis have been accepted as a form of therapy for renal failure in Singapore. The spin off from the creation of dialysis units has been improvement in overall renal care particularly in cases of acute renal failure. It has also generated an atmosphere for research into renal diseases and has helped to promote the image of Singapore as a medical centre par excellence in Southeast Asia.

Polycythaemia after renal transplantation.

The haematological, biochemical and clinical features of six patients with polycythaemia after renal transplantation were studied. The patients had an absolute increase in red cell mass, but normal plasma and whole blood volumes. Primary proliferative polycythaemia was excluded. Polycythaemia developed within one year of transplantation and persisted for 3-7 years. Chronic rejection, renal artery stenosis, severe hypertension and corticosteroid therapy were probably not the cause of the polycythaemia. There were no occlusive vascular lesions during the observation period and venesections were generally not required. The polycythaemia is probably the result of the cumulative production of erythropoietin by the donor and recipient kidneys.

Glomerulonephritis in Singapore: an overview.

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.

Nephrotic syndrome associated with malignant tumours.

The nephrotic syndrome complicating malignancy is an unusual occurrence. We report here four cases of nephrotic syndrome associated with malignant tumours. Three cases were associated with bronchogenic carcinoma and one with adenocarcinoma of colon. One of the four cases developed nephrotic syndrome before the discovery of bronchogenic carcinoma. All patients had renal biopsies with light microscopy, immunofluorescence and electron microscopy. The findings suggest an immune-complex disease complicating malignancy. The true incidence of nephrotic syndrome associated with malignant tumours is unknown. However it is clinically prudent to screen for malignancy in older patients presenting with nephrotic syndrome.

Serum ionized calcium in nephrotic syndrome.

Serum ionized calcium was measured in 12 patients with nephrotic syndrome and 14 nephrotic patients during clinical remission. All subjects had normal creatinine clearance and were not receiving treatment at the time of study. The mean serum ionized calcium values of the two groups of patients, 1-08 +/- 0-10 (SD) mmol/l ultrafiltrate and 1-21 +/- 0-10 (SD) mmol/l ultrafiltrate respectively, are significantly lower than the normal mean (1-28 +/- 0-06 (SD) mmol/l ultrafiltrate). The mean values of the patients in remission is, however, significantly higher (P less than 0-005) than that of the patients with manifest nephrotic syndrome. Elevated serum complexed calcium, and high serum protein-bound calcium in relation to serum albumin, were encountered, being more apparent in patients with overt nephrotic syndrome.

Calcium and phosphorus metabolism in nephrotic syndrome.

Calcium and phosphorus balance studies were performed on 13 nephrotic patients and eight patients during clinical remission of the nephrotic syndrome. Marked impairment of intestinal absorption of calcium was found among nephrotic patients, in eight of whom faecal calcium equalled or exceeded dietary calcium. The mean faecal:dietary calcium ratio of nephrotic patients, 1-06 +/- 0-23 (SD), was significantly higher (p less than 0-005) than that of patients in remission, 0-58 +/- 0-21 (SD). The mean 24-hour urinary excretion of calcium of nephrotic patients, 0-68 +/- 0-68 (SD) mmol, was significantly lower (p less than 0-005) than that of patients in remission, 3-02 +/- 1-91 (SD) mmol. Calciferol administered to three nephrotic patients in the dosage of 1.25 mg per day did not significantly influence intestinal absorption or renal excretion of calcium. There was no difference between the two groups of patients in intestinal absorption or renal excretion of phosphorus; there was net intestinal absorption in all subjects. Quantitative bone histology was studied in seven of the nephrotic patients. None had osteomalacia or osteitis fibrosa, while only one had evidence of mild osteoporosis.

Protein selectivity in IgA nephropathy.

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.