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.

99Tcm-(tin) colloid scans in the evaluation of renal transplant rejection.

Technetium-99m-(tin) colloid uptake in renal transplants was quantified to evaluate rejection. A dynamic acquisition following i.v. injection of 110 MBq of this radiopharmaceutical enabled quantification of 15 to 20 min transplant uptake (PU), in terms of percentage of an injected dose after allowing for attenuation in the patient. An uptake ratio (UR) i.e. the ratio of 15 to 20 min uptake over the 0 to 5 min uptake was also derived. Normal values were obtained in 20 stable functioning transplants (normal PU less than or equal to 1%, normal UR less than or equal to 0.7). In 66 patients, PU and UR were compared with clinical, biochemical, histological and radiological, evidence of rejection. A sensitivity of 70% and specificity of 85% was obtained for this 99Tcm-(tin) colloid study in the diagnosis of renal transplant rejection.

Studies on the anaemia of Asian patients with chronic renal failure undergoing regular haemodialysis.

Studies of ferrokinetics, iron status and serum erythropoietin levels were undertaken in 28 Asian patients on RDT as they appeared to be more anaemic and to have a poorer response to treatment than their Western counterparts. The main aetiological factor seemed to be inadequate bone marrow function which tended to be worst in those who had been on dialysis the longest. In addition it is possible that there was also a relative lack of erythropoietin. Dietary factors and iron deficiency were not important. The possible roles of a progressive accumulation of a toxic factor, or of relative underdialysis in patients who were profoundly uraemic prior to the institution of regular haemodialysis, are discussed.

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.

Five cases of arsine poisoning.

Arsine is one of the most potent haemolytic agents found in industry. Four workers presented with abdominal pain, jaundice and passing tea-coloured urine. A fifth worker also passed dark urine but had no other symptoms. Investigation revealed that all five workers were from a tin smelting plant where they were involved in mixing tin ore with dross. They were exposed to arsine gas after mixing a particularly large quantity of dross with tin ore which was wet because of rain. Three of the cases developed renal impairment and also a mild sensory neuropathy. All survived with proper management in hospital which included exchange blood transfusions, and peritoneal dialysis where indicated. Prevention of such poisoning includes keeping dross away from all moisture, good ventilation in work areas, and adding dross directly to the furnace.

Leucocyte cation transport in essential hypertension: its relation to the renin-angiotensin system.

Leucocyte cation transport measured when patients received a normal sodium intake and the response of the renin-angiotensin system to changes in sodium intake were studied in 22 patients with essential hypertension. The rate constant for total leucocyte sodium efflux measured during a normal diet was significantly correlated with the plasma renin activity measured during a low sodium diet. Impairment of leucocyte sodium transport was significantly greater in eight patients whose plasma renin activity failed to rise into the normal range during the low sodium diet as compared with the 14 other patients, whose renin system responded normally to sodium restriction. These results provide further suggestive evidence for the hypothesis that there is a circulating sodium transport inhibitor that may be important in the pathogenesis of essential hypertension.

Renal tuberculosis presenting with accelerated hypertension.

Hypertension is an uncommon complication of renal tuberculosis, and the association of accelerated hypertension with renal tuberculosis has not hitherto been documented in the literature; we present such a case. The diagnosis of renal tuberculosis may be difficult, particularly in the early stages of the disease, and in this case diagnosis was made by renal biopsy. The subsequent course of the patient was also particularly interesting, in that one year after starting treatment with anti-tuberculosis and anti-hypertensive medication, he developed sarcoidosis.

Effect of radiocontrast media on kidneys of patients with renal disease.

A prospective study was undertaken of 15 patients with impaired renal function undergoing x-ray procedures entailing the use of contrast material to see whether any deterioration in renal function resulted. Patients with diabetes or myelomatosis were excluded. Detailed observations were made during three days before and after the x-ray procedure to detect any change in factors such as fluid state, drug treatment, infection, or diet which might have affected renal function. No significant changes occurred in endogenous creatinine and 51Cr-EDTA clearances, or in plasma creatinine and urea concentrations after the x-ray procedures. Furthermore, there was no change in urinary activity of N-acetyl-beta-D-glucosaminidase, which is a highly sensitive indicator of renal parenchymal damage. Provided that fluid depletion and multiple x-ray procedures with radiocontrast material in rapid sequence are avoided, these procedures do not appear to affect renal function adversely, even when renal disease is advanced.

Abnormal leucocyte composition and sodium transport in essential hypertension.

Cation transport and electrolyte composition were studied in leucocytes from 17 patients with uncomplicated essential hypertension. Significant increases in cell sodium and water contents, associated with a depression of the rate-constant for active sodium efflux, were found in the hypertensive patients. These abnormalities in cell sodium transport may possibly be related to mechanisms of hypertension.

Abnormal sodium transport in leucocytes from patients with essential hypertension and the effect of treatment.

1. In seventeen patients with untreated essential hypertension the sodium and water contents of leucocytes were significantly increased, whereas the rate constant for ouabain-sensitive sodium efflux was significantly reduced. 2. These abnormalities were not found in fourteen other patients with well-controlled hypertension. 3. Preliminary observations in accelerated hypertension suggest a different pattern of abnormality in leucocyte sodium metabolism.

The effect of external potassium concentration on leucocyte cation transport in vitro.

1. Sodium and potassium transport rates in human leucocytes were measured in vitro at different external potassium concentrations. 2. At nominally zero external potassium concentrations, the ouabain-sensitive sodium efflux was reduced to less than 20% of its maximum value. There was evidence that under these conditions a ouabain-sensitive sodium-sodium exchange occurs. 3. Both total and ouabain-insensitive potassium influx increased with increasing external potassium concentration. The ouabain-sensitive potassium influx showed saturation. 4. Ouabain-insensitive potassium efflux was also stimulated by increasing the external potassium concentration, suggesting significant potassium-potassium exchange at physiological external potassium concentrations.

Leucocyte sodium transport in uraemia.

1. In sixteen patients with severe chronic renal failure the rate constant for total sodium efflux from leucocytes was significantly reduced compared with that in thirty control subjects. This difference lay chiefly in the glycoside-sensitive ('active') moiety of sodium efflux. 2. In sixteen patients receiving regular haemodialysis, the rate constant for total sodium efflux from the leucocyte was significantly greater than in the undialysed uraemic patients though still subnormal. 3. In individual patients, an increase in sodium efflux could be detected as early as 1 week after regular haemodialysis was started. 4. These results are compatible with the existence of a dialysable molecule in uraemic plasma affecting leucocyte sodium transport.

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.