Thrombotic microangiopathy following renal ischaemia and revascularization: apoptosis of endothelial cells in action.
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Biomedical subjects
Publications and source records attributed to L Nolin.
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The condition known as IgA nephropathy was first identified when Berger observed mesangial staining for IgA in healthy patients with isolated hematuria. These patients often presented with recurrent synpharyngitic hematuria or less frequently with asymptomatic microscopic hematuria and proteinuria. Although initially considered benign, we now recognize it as a common cause of end-stage renal failure. The overall prognosis may be better than suggested in the literature, as patients with mild asymptomatic hematuria are often not biopsied and, therefore, frequently are not included in published articles. We reviewed prospective and retrospective adult studies published after 1976 and analyzed them to produce evidence-based recommendations. Patients with proteinuria over 3 g/day, mild glomerular changes only, and preserved renal function (creatinine clearance over 70 ml/min) should be treated with prednisone. Steroids reduce proteinuria (grade B recommendation) and stabilize kidney function (grade C). The combination of cyclophosphamide, dipyridamole and warfarin should not be used (grade A), nor should cyclosporine A (grade B). In patients with progressive disease (creatinine clearance of less than 70 ml/min), fish oil should be given (grade B). A tonsillectomy could reduce proteinuria and hematuria in those patients with recurrent tonsillitis (grade D). Those with hypertension should be treated promptly with an angiotensin-converting enzyme inhibitor (grade B).
Thirty-eight intensive care unit (ICU) patients (26 men and 12 women with a mean age of 57.0 +/- 16.6 years) with acute renal failure (ARF) treated by venovenous continuous renal replacement therapy (CRRT) were evaluated while in relatively steady metabolic control. Twenty-seven were undergoing continuous venovenous hemodialysis, nine were undergoing continuous venovenous hemodiafiltration, and two were undergoing continuous venovenous hemofiltration. Periods of analysis varied between 24 and 408 hours (mean duration, 82.7 +/- 70.6 hours; median, 72 hours). Their mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score within 24 hours of admission to the ICU was 21.3 +/- 6.3 and survival rate was 31.6%. Urea nitrogen and creatinine concentrations were determined every 6 to 12 hours in both serum (Cun and Cc, respectively) and effluent (spent dialysate and/or ultrafiltrate). The mean effluent rate was 1,472 +/- 580 mL/h and blood flow rate, 166 +/- 32 mL/min. Urine was collected daily for urea nitrogen and creatinine measurement. Urea nitrogen appearance rate (UnA) and creatinine production rate (Pc), calculated from urea nitrogen (UnMR) and creatinine mass removal (CMR) from both the effluent and the urine, using Garred mass balance equations and the Forbes-Bruining formula, allowed normalized protein catabolic rate (nPCR) and estimates of lean body mass (LBM) to be derived. Creatinine metabolic degradation rate (Dc), estimated by the Mitch formula, was included in the calculation. The lowest body weight recorded during the study period was considered as dry weight (BW). The creatinine index (CI) was also obtained. For each parameter, the results are presented as mean, median, and range values: UnMRe (from effluent), 13.6 +/- 7.2, 12.5, 1.6 to 32.6 mg/min; UnMRu (from urine), 0.13 +/- 0.40, 0, 0 to 2.30 mg/min; UnA, 13.6 +/- 7.0, 12.5, 3.8 to 32.1 mg/min; nPCR, 1.75 +/- 0.82, 1.60, 0.61 to 4.23 g/kg/d; CMRe (from effluent), 942.0 +/- 362.3, 918.0, 211.2 to 1,641.6 mg/d; CMRu (from urine), 44.4 +/- 138.8, 0, 0 to 698.5 mg/d; Dc, 94.6 +/- 49.9, 81.9, 31.0 to 294.1 mg/d; Pc total, 1,067.1 +/- 409.7, 1,053.7, 261.5 to 1,988.2 mg/d; LBM, 38.3 +/- 11.9, 37.9, 15.0 to 65.0 kg; LBM/BW ratio, 49.5% +/- 14.0%, 50.3%, 22.5% to 86.0%; and CI, 13.7 +/- 4.7, 14.2, 4.1 to 25.8 mg/kg/d. When Pc was estimated from the Cockcroft-Gault equations (as Pc'), the mean value for Pc and Pc' was similar (1,067.1 +/- 409.7 v 1,284.9 +/- 484.1 mg/d), but there were relatively large differences for the majority of cases. A positive correlation was observed between UnA and Pc (R = 0.42). Serum albumin and LBM/BW correlated poorly (R = 0.20). Outcome was weakly related to UnA and to nPCR (R = 0.29 and R = 0.31, respectively). Urea nitrogen appearance appears widely variable in critically ill ARF patients. This simple approach can provide useful information for an easy estimate of net protein catabolism in critically ill patients with ARF undergoing CRRT.
Although ammonium acid urate (AAU) stones are endemic in Asia, pure AAU calculi have almost disappeared from industrialized countries and clinical pathophysiologic relevance of sporadic stones containing AAU crystals is currently unknown. We reviewed 1,396 crystallographic stone analyses performed in our institution over a 10-year period. Prevalence of stones containing AAU crystals and predominantly AAU stones were 3.1% and 0.2%, respectively. In more than two thirds of cases, AAU crystals represented less than 10% of stone crystal composition. No pure AAU stone was found. According to crystalline predominance, 42%, 35%, and 12% of these calculi were uric acid, infectious, and calcium oxalate stones, respectively. AAU crystals were detected as discrete intercrystalline or peripheral deposits in 74.4% of stones. In only one calculus was AAU crystals detected in the nucleus. The hospital charts of 37 patients who presented with 43 calculi containing AAU crystals were also reviewed. The mean age was 53.1 +/- 16.6 years. Fifty-seven percent of calculi were upper urinary tract stones and 43% were bladder stones. Upper urinary tract calculi were more frequently uric acid stones, followed by infectious and calcium oxalate stones. Lower urinary tract calculi were more frequently infectious stones, followed by uric acid stones. Upper urinary tract stones were passed spontaneously in 13 patients and removed surgically in nine patients. Nine of these subjects were idiopathic recurrent stone formers who had passed other calculi with no trace of AAU crystal. Fifty-seven percent of lower urinary tract stones were associated with documented bladder dysfunction. In conclusion, although AAU-containing urolithiases are occasionally seen in our population, predominantly or primarily AAU stones are exceptional. AAU crystal formation usually appears as a minor and secondary phenomenon of no primary pathophysiologic relevance in stone formation.
To better define the survival and quality of life of patients with major left ventricular systolic dysfunction and end-stage renal disease treated by continuous ambulatory peritoneal dialysis (CAPD), we reviewed all cases who started CAPD between May 1984 and March 1993 who had an isotopic left ventricular ejection fraction (LVEF) < or = 35%. Seventeen patients (12 men and five women with a mean age of 51.6 +/- 14.9 years) met the inclusion criteria. Mean isotopic LVEF before initiation of CAPD was 24.8% +/- 8.2%. All patients were symptomatic from congestive heart failure. Thirteen patients were classified as New York Heart Association grade III or IV. Continuous ambulatory peritoneal dialysis was associated with a significant improvement of isotopic LVEF, of functional status, and of blood pressure control. In 10 patients with a second measurement on CAPD, LVEF increased from a mean value of 23.2% +/- 9.1% to a mean value of 30.3% +/- 8.1% (P < 0.01). This represents a 30% increase of LVEF. After 6 months on CAPD, 94% of patients were classified as New York Heart Association grade I or II. Actuarial survival rates were 94%, 80%, and 64% at 12, 18, and 24 months, respectively. The mean duration of CAPD was 24 +/- 17 months. These results suggest that current CAPD treatment is an elective modality of treatment in patients with concomitant heart and renal failure.
In an era of increasing scrutiny regarding use of health care resources, it is critical that physicians have rational, evidence-based guidelines for treatment decisions. This review of more than 200 published papers constitutes a comprehensive approach to evaluating the current evidence regarding the clinical use of recombinant human erythropoietin therapy in renal failure patients. After this review, specific recommendations are provided regarding who should receive r-HuEPO; what the target hemoglobin should be; the best route of administration of r-HuEPO; how iron status should be evaluated and managed; and monitoring and follow-up of patients taking r-HuEPO. Throughout the article, areas for important future research are also identified.
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One hundred one continuous ambulatory peritoneal dialysis (CAPD) patients from a single North American center were analyzed in a retrospective and cross-over study for peritonitis rates using a standard system (Travenol System II) or a Y-shaped disconnect-disinfectant system (Travenol O-set). Twenty-one of 34 patients using the standard set (group I) had 53 episodes of peritonitis in 508 patient-months or one episode per 9.6 patient-months. Nine of 17 patients switching from the standard to the disconnect-disinfectant system (group II) experienced 22 episodes of peritonitis in 275 patient-months or one episode per 12.5 patient-months on the standard set, while six patients had 10 episodes of peritonitis in 275 patient-months or one episode per 27.5 patient-months on the disconnect-disinfectant system (P less than 0.04). Twenty-eight of 67 new CAPD patients starting on the disconnect-disinfectant system (group III) had 37 episodes of peritonitis in 1,086 patient-months or one episode per 29.4 patient-months (P less than 0.01 v group I). Exit-site infections (ESI) occurred in 35.3% of patients using the standard set versus 34.3% of those using the O-set. The presence of an ESI was not associated with a higher risk of peritonitis, but modified the bacteriological profile of subsequent peritonitis episodes in patients using the O-set, favoring the organisms isolated from the exit site. Decreases in peritonitis rates with the O-set were due to a reduction of peritonitis episodes secondary to most bacterial agents and not only to skin organisms. Diabetics using intraperitoneal insulin had similar peritonitis and ESI rates as nondiabetics.(ABSTRACT TRUNCATED AT 250 WORDS)
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The mechanism of the GN induced by the intravenous injection of antibodies directed against renal tubular epithelial antigens (RTE) was studied by the use of antibody specifically purified by affinity chromatography. With this reagent RTE antigens could be demonstrated on frozen sections of glomeruli as well as on glomerular cells in culture. The antibodies were radiolabelled, and using paired label techniques glomerular binding could be measured in vivo. In normal rats, approximately 4% of the antibody injected was specifically bound in the glomeruli. Binding was not detectable on proximal tubular brush borders. In rats treated with 100 mg/kg of aminonucleoside of puromycin, a substance known to induce alterations of glomerular epithelial cells, it could be shown that glomerular binding was selectively decreased. These observations indicate that immune deposits in passive Heyman nephitis are formed mainly in situ and that local alteration of the glomerulus can markedly influence deposit formation.
Subacute sclerosing panencephalitis (SSPE) is a progressive neurologic disease associated with chronic measles infection. We have assessed renal function parameters and renal biopsy details in 14 patients with SSPE. All had normal renal function. However, 9 had microscopic hematuria. 9 patients had focal segmental mesangial proliferation and 5 had capillary wall thickening with deposits visible by light microscopy. 13 patients had glomerular C3 deposition and 4 had IgG deposits. SSPE is a disease caused by chronic viral infection, in which nephritogenic complex formation may occur.
Ultrastructural and immunofluorescent microscopic studies were performed on renal tissue obtained from nine patients during the acute and convalescent phase of the haemolytic uraemic syndrome (HUS). All had glomerular deposits of IgM in the absence of circulating immune complexes. This was associated with deposition of C1q during the acute phase, and properdin and C3 during the convalescent phase. C4 was consistently absent. Since such a pattern of complement deposition does not fulfil criteria either for alternate or classical pathway activation, the possibility of C1q bypass loop activation by IgM is suggested.
Minoxidil, a new potent hypotensive agent, was used as the primary antihypertensive agent in 11 patients--10 men and 1 woman aged 35 to 54 years with severe hypertension that was refractory to treatment with maximal (or maximally tolerated) doses of conventional antihypertensive agents. Six patients had severely impaired renal function and three of them were undergoing long-term hemodialysis. The patients were given 2.5 to 40 mg/d of minoxidil for periods of 2 to 29 months. All except one who was almost anuric received propranolol and diuretics. Blood pressure was controlled satisfactorily in all patients. In two patients the hypertension became partially resistant after 1 year of treatment. The main side effects were sodium retention, tachycardia and hirsutism. Renal function remained stable or improved and hemodialysis was discontinued in two patients. Minoxidil is a remarkably potent hypotensive with relatively few side effects and seems particularly advantageous in patients with chronic renal failure.
Intra-access flow (Qac), measured by ultrasound dilution, is a reliable method for screening for access dysfunction. Because of a reduced circulating volume and a relative decrease in blood pressure at the end of hemodialysis (HD), we hypothesized that Qac could be significantly reduced when measured late into HD. Fifty patients were prospectively evaluated for variation in Qac early and late into HD. There were 33 native fistulae and 17 synthetic grafts. Six separate measures of Qac were performed for each patient by ultrasound dilution (Transonic HD01 hemodialysis monitor; Transonic Systems, Inc., Ithaca, NY): three within the first 30 minutes and three within the last 30 minutes of HD. Session time was 3.5 or 4 hours, and mean net ultrafiltration was 3.3 +/- 0.9 L/HD. Early and late into HD, mean arterial pressure (MAP) decreased from 100.0 +/- 14.6 to 92.8 +/- 17.8 mm Hg, heart rate from 73 +/- 11 to 79 +/- 15 bpm, and hematocrit increased from 34 +/- 3 to 38 +/- 4%. For the whole group, mean Qac decreased from 1,101.7 +/- 566.7 to 972.5 +/- 515.6 ml/min (p = NS); when Qac was corrected for a MAP of 100 mm Hg, the reduction remained nonsignificant (from 1,101.7 to 1,048.0 ml/min). When considering native and synthetic fistulae separately, the drop in Qac was still nonsignificant (from 1,098.9 +/- 613.4 to 983.2 +/- 593.2 for native fistulae versus 1,107.2 +/- 480.5 to 999.8 +/- 379.8 ml/min for grafts, p = NS). Overall, the percent reduction in Qac early versus late into HD was 11.7%, whereas it reached only 4.9% when access flows corrected for MAP were considered. We conclude that variation in Qac during HD is relatively small, especially when values are corrected for MAP. Therefore, according to our results, Qac measures by using the ultrasound dilution method made at any time during HD should be reliable for most patients.
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