J. Levi

Castration inhibits glomerular hypertrophy and proteinuria in uninephrectomized male rats

Abstract. Renal mass reduction may lead to glomerular hypertrophy, proteinuria and focal glomerulo‐sclerosis (FGS) in humans and rats. In humans and rats, females are less susceptible than males to these phenomena. This study was undertaken to evaluate the effect of male rat castration on the pathogenesis of proteinuria and FGS. Urinary protein was measured in 60‐day‐old male and female rats. Uninephrectomy was performed in all rats, and castration in half of the males. After 180 days, proteinuria, glomerular filtration rate (GFR) and blood biochemistry were determined. Kidneys were resected, weighed and subjected to morphologic studies. Following uninephrectomy, male rats developed severe proteinuria:132.3 pM 40.9 mg 24 h‐1, most of which was accounted for by an albuminuria of 70.9 pM 19.3 mg 24 h‐1. In contrast, protein excretion in female and castrated male rats remained within normal limits: 8.0 pM 1.8 and 4.2 pM 0.5 mg 24 h‐1, respectively. Mean glomerular volume in male rats was 1.18 pM 0.08 times 106μm3; much higher than in female rats, 0.84 pM 0.04 times 106μm3, and castrated male rats, 0.87 pM 0.03 times 106μm3 (P<0.005). On light and electron microscopy, glomeruli of female and castrated male rats were completely normal. In contrast, in four of seven male rats, mild glomerular changes were observed. They consisted mainly of mesangial expansion, electron‐dense deposits and collapse of capillary loops. These data suggest that castration confers protection against the development of glomerular hypertrophy and proteinuria in uninephrectomized male rats. Endogenous testosterone may be associated with this development.,

Platelet Count and Thrombopoietic Activity in Patients with Chronic Renal Failure

The frequency of thrombocytopenia in patients with chronic renal failure (CRF) is controversial. This study was undertaken to investigate the platelet count in 55 patients with end-stage renal disease on maintenance hemodialysis and in 19 patients with CRF before hemodialysis had begun. In both groups platelet counts were similar and significantly reduced, 175,000 +/- 6,500 and 181,000 +/- 10,800 compared to 253,000 +/- 3,700/mm3 in the control (p less than 0.0001). 31% of hemodialysis patients had thrombocytopenia (platelet count less than 150,000/mm3). The megakaryocyte number in their bone marrow aspirate was not reduced. Primary renal disease, androgen treatment or parathyroidectomy did not affect the platelet count. Thrombopoietic activity using 75Se-selenomethionine incorporation into platelets measured in 7 thrombocytopenic patients was found to be reduced, 6.77 +/- 0.29 vs. 9.06 +/- 0.27 (X 10(-2)%: p less than 0.001). This study shows that the platelet count is reduced and mild thrombocytopenia is frequent in patients with CRF. A possible cause for the platelet count reduction is insufficient thrombopoietic activity.

Erythrocytosis Associated with Renal Artery Thrombosis in a Patient with Polycystic Kidney Disease on Hemodialysis

We report a case of erythrocytosis in a patient with end-stage renal failure on chronic hemodialysis. The patient with polycystic kidney disease had an average Hb level of 10 g/dl while on hemodialysis for 3 years. He developed erythrocytosis (Hb 17.6 g/dl) following a cadaveric renal transplantation. No signs suggesting polycythemia vera were found. Nonrenal causes of secondary erythrocytosis such as anoxia, hemoglobinopathies or tumors were excluded. Angiography showed renal artery occlusion of the native kidney. Serum erythropoietin level was 85 U/l (normal 52 +/- 31 U/l) as measured by 3H-thymidine uptake. It is suggested that ischemia caused by the renal artery thrombosis stimulated the erythropoietin production in the native polycystic kidney.

Parathyroid hormone effect on the fragility of human young and old red blood cells in uremia.

Parathyroid hormone (PTH) is elevated in patients with chronic renal failure (CRF) and was suggested to be one of the factors responsible for the anemic syndrome of these patients because it raises the osmotic fragility of the red blood cells (RBC). In the present study, the youngest and oldest RBC were separated from circulating erythrocytes by high-speed centrifugation. The age distribution was described, and the effect of PTH on the different age groups was investigated. Median density (MD) and glutamic-oxaloacetic transaminase (GOT) activity were chosen as age markers. MD (1.0985 +/- 0.00087) and GOT activity (12.49 +/- 2.083 IU/g Hb) of the young uremic cells did not differ significantly from the values of young normal cells (1.0987 +/- 0.00046 and 10.36 +/- 1.174 IU/g Hb, respectively). The MD of the oldest cells, however, was lower (1.1048 +/- 0.00054) and GOT was higher (6.60 +/- 1.1019 IU/g Hb) in the uremic than in the control cells (1.1093 +/- 0.00175 and 3.77 +/- 0.233 IU/g Hb, respectively). These results indicate that the life span of RBC in uremics is shorter than normal and that an enrichment of circulating RBC by young cells occurs in uremic patients. The median osmotic fragility (MOF) of the young cells was lower in both uremic (0.376 +/- 0.006) and control patients (0.378 +/- 0.003) than the MOF of old cells (0.402 +/- 0.005 and 0.392 +/- 0.004, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Enalapril Attenuates Glomerular Hyperfiltration following a Meat Meal

It has been shown that the glomerular filtration rate increases after a meat meal. We examined in humans whether enalapril, which has been shown to decrease glomerular capillary pressure in rats with chronic renal failure, could attenuate the renal response to a meat meal. Twelve healthy volunteers were studied after an oral protein load, 1.5 g/kg body weight, as lean cooked beef meat, and on a separate day, after eating the same meal with prior oral intake of enalapril. On the control day, creatinine clearance increased from 114.3 +/- 4.7 before the meal to 137.1 +/- 4.7 ml/min/1.73 m2 after the meal (p less than 0.001). On the enalapril intake day, creatinine clearance increased from 113.7 +/- 5.6 before the meal to 128.3 +/- 5.8 ml/min/1.73 m2 after the meal (p less than 0.01). However, the mean increase in creatinine clearance was lower on the enalapril intake than on the control day (14.0 +/- 4.3 vs. 21.0 +/- 4.1%, p less than 0.05). Mean arterial pressure before the meal was lower on the enalapril intake day than on the control day (76.2 +/- 3.5 vs. 84.2 +/- 3.6, p less than 0.01). Likewise, postprandial mean arterial pressure was lower on the enalapril day compared with the control day (69.9 +/- 2.8 vs. 78.5 +/- 3.7, p less than 0.01). We conclude that enalapril blunts the hyperfiltration which follows a meat meal.

Brainstem Auditory Evoked Responses in Chronic Renal Failure and the Effect of Hemodialysis

Brainstem auditory evoked responses (BAER) were recorded in patients with chronic renal failure before commencement of chronic dialysis treatment, and in patients with end-stage renal failure on chronic hemodialysis for several years. Both groups of patients had delayed latencies of the third and fifth waves. The patients on hemodialysis revealed delayed latency of interpeak I-V as well. There was no correlation between wave latency, serum urea, creatinine, PTH or duration of chronic hemodialysis treatment. A hemodialysis session led to a slight shortening of the third wave. This study suggests that neural conduction along the brainstem in patients with chronic renal failure is delayed even before hemodialysis is started. Although 1 dialysis session may have some beneficial effect, long-term hemodialysis treatment does not seem to shorten the delay in neural conduction observed in patients with chronic renal failure.

Effect of Long-Term Aluminum Administration on the Renal Structure of the Rat

Kidneys of patients on hemodialysis therapy often undergo structural changes leading to acquired cystic disease. A wide variety of chemical compounds are known to induce experimental renal cystic disease. Since aluminum intoxication has been implicated in the development of encephalopathy, osteomalacia and anemia in uremic patients, this study was designed to investigate whether aluminum administration to normal rats could induce renal morphological changes. Male Wistar rats were divided into three groups; Animals of the Low-dose aluminum (LDA) group received 0.2 mg/day of aluminum, animals of the high-dose aluminum (HDA) group received 2 mg/day of aluminum; the third group consisted of controls (C). Aluminum was injected intraperitoneally as aluminum chloride (6 days a week). 13 weeks later, the kidneys were removed and examined by light and electron microscopy. The findings on eight-microscopic examination were normal in all groups. Electron-microscopic examination was unremarkable in the C and LDA group. In HDA rats, ultrasections of the cortex and outer medulla showed changes in the proximal tubules with increased size and number of lysosomes, osmiophilic granular material inside the lysosomes, vacuolisation of organelles and mitochondrial damage of varying degree. No cystic changes were found.

Uninephrectomy Aggravates Tubulointerstitial Injury in Rats with Adriamycin Nephrosis

The effects of uninephrectomy on the function and structure of the remnant kidney were assessed in rats with Adriamycin-induced nephrosis, 12 weeks after the injection of Adriamycin. The kidney volume of Adriamycin-treated uninephrectomized rats (NX-AD) was 2.3 times that of sham-operated, Adriamycin-treated animals (SH-AD; p < 0.001). The marked renal enlargement in NX-AD animals was due to the development of large tubular cysts. Following uninephrectomy, the fractional volume of tubular lumen almost doubled (NX-AD, 0.33 +/- 0.02; SH-AD, 0.17 +/- 0.02; p < 0.001) and the absolute volume of tubular lumen increased more than fourfold (NX-AD, 0.51 +/- 0.08 ml; SH-AD, 0.12 +/- 0.02 ml; p < 0.001). The frequency of tubular lumen with a large cross-sectional area (> or = 40,000 microns 2) was 5.8 +/- 1.1% in NX-AD and 0.7 +/- 0.2% in SH-AD groups (p < 0.001). The fractional volume of interstitial fibrosis in NX-AD animals was larger than in SH-AD (0.09 +/- 0.02 versus 0.04 +/- 0.01%, p < 0.05). As opposed to the worsening of tubulointerstitial disease, single-kidney glomerular filtration rate, fractional protein clearance, glomerular volume and the extent of glomerular sclerosis did not differ significantly in NX-AD as compared to SH-AD groups. This study shows that uninephrectomy in rats with Adriamycin nephrosis worsens interstitial nephrosis and aggravates the formation of tubular cysts, leading to a macrocystic kidney disease. These changes are not associated with an increase in glomerular sclerosis.

Increased RNA and Heme Synthesis in Mouse Erythroid Precursors by Parathyroid Hormone

The in vitro effect of parathyroid hormone (PTH) on RNA and heme synthesis by embryonic mouse liver erythroid precursors was examined. PTH produced a dose-dependent effect on RNA synthesis. A maximal increase of 60 +/- 16% (p less than 0.02) was observed with 1.0 U PTH/ml, whereas with higher concentrations a significant decline was found. Furthermore, PTH stimulated heme synthesis after 24 h of incubation. The maximal enhancement of 32 +/- 7% (p less than 0.01) was observed with 0.5 U PTH/ml, a lower effect was obtained with 1.0 U PTH/ml, while 2.0 U PTH/ml caused a pronounced decrease of heme synthesis. These data indicate that PTH affects directly the erythroid precursors by a mechanism similar to that of erythropoietin. The inhibitory effect on the RNA synthesis observed with large doses of PTH may explain at least one of the causes of the anemia reported in patients with primary hyperparathyroidism.

Acute renal failure in a solitary kidney due to bacterial pyelonephritis.

Deterioration of renal function after acute bacterial pyelonephritis is rare. We report on 2 patients with a solitary functioning kidney in whom acute renal failure developed in the setting of acute bacterial pyelonephritis. Following antimicrobial treatment kidney function returned to baseline values. This finding suggests that patients with a solitary functioning kidney are more prone to have renal dysfunction after acute bacterial pyelonephritis.