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Biomedical subjects

G Keusch

Publications and source records attributed to G Keusch.

At least 19 recordsLinked to original sources

[Supportive medical management of patients with chronic renal failure].

Progressive renal failure occurs in a large number of patients even in the absence of the original cause of injury. It is suggested that the initial reduction in nephron number progressively damages the remaining ones. Various mechanisms underlie the pathogenesis of progressive glomerular injury. Several studies have extensively shown that both dietary protein restriction and pharmacologic intervention with ACE-inhibitiors and angiotensin receptor antagonists effectively slow the progression of chronic renal diseases. This article will present treatment recommendations designed to delay the progression of chronic renal disease, to optimize its medical management and to reduce complications induced by renal insufficiency including hypertension, renal osteodystrophy and anemia. Ten steps in the management of patients with chronic renal failure recommended by an international panel of experts based on existing guidelines are presented.

Anemia↗

Malaria.

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Child↗

Calciphylaxis: a syndrome of skin necrosis and acral gangrene in chronic renal failure.

BACKGROUND: Calciphylaxis is a rare condition of rapidly extending ischemic skin necrosis or acral gangrene of fingers, toes or penis in patients with chronic renal failure. It may be accompanied by extensive metastatic calcification of soft tissues. Histology of infarcted tissues shows prominent medial calcification and intimal hyperplasia of subcutaneous arteries and/or digital arteries, respectively. The pathogenesis of calciphylaxis is only poorly understood. Most patients have hyperparathyroidism and an elevated calcium-phosphate-product, which is thought to be a major pathogenetic factor of calciphylaxis. PATIENTS AND METHODS: All published cases of calciphylaxis including nine of own (155 patients in total) from 1936 through 1996 were reviewed and subjected to statistical meta-analysis (Fisher's exact test). RESULTS: Proximal locations of necrosis (thighs, buttocks, trunk) carried an unfavourable prognosis (63% mortality) compared to distal locations (calves, forearms, fingers, toes, penis) with 23% mortality (p < 0.0001). Parathyroidectomy was associated with a favourable outcome (p < 0.004). Diabetics with chronic renal failure had acral gangrene in 61% compared to 34% of the non-diabetic calciphylaxis-patients (p < 0.007). CONCLUSIONS: The present analysis of all published cases of calciphylaxis is limited by patient selection and publication bias. The unfavourable prognosis of patients with proximal necrosis is impressive and might justify an early and aggressive treatment in such cases. However, the general benefit of parathyroidectomy remains debatable. Hyperparathyroidism should be managed primarily by conservative means. Parathyroidectomy should be reserved for patients with very high parathyroid hormone level and calcium-phosphate-product or with a rapidly progressive disease.

Calciphylaxis↗

[Creatinine of 250 micro mol/l: what should be done?].

This article aims at guidelines for evaluation of an accidentally detected increase of creatinine levels in serum and the decision if and when hospitalisation is mandatory. Hospitalisation is indicated when the general condition is poor and clinical signs of uremia like pericarditis, encephalitis, pulmonary edema with cliguria or anuria and severe hyperkalaemia or metabolic acidosis exist. In other cases an outpatient evaluation is possible yielding often information on preexisting risk factors, that may lead to functional renal failure, by history and clinical investigation. Furthermore assignment of the actual renal failure to a prerenal, renal or postrenal cause, usually by means of ultrasound and therapeutic consequences are demonstrated. A tabular overview on pathogenesis and gradation of various forms of acute renal failure and their identification by findings in urine sediments and/or chemical urine analysis is given.

Acute Kidney Injury↗

Pharmacokinetics of antimicrobial agents in anuric patients during continuous venovenous haemofiltration.

BACKGROUND: The optimal drug dosing in anuric patients undergoing continuous haemofiltration is a difficult task. More pharmacokinetic data is needed to derive practical guidelines for dosage adjustments. METHODS: Drug elimination of various antimicrobial agents (amikacin, amoxycillin, ceftazidime, ciprofloxacin, flucloxacillin, imipenem, netilmicin, penicillin G, piperacillin, sulphamethoxazole, tobramycin, vancomycin) was studied in 24 patients with acute renal failure treated by pump-assisted continuous venovenous haemofiltration (CVVH). Concentrations of serial blood and ultrafiltrate samples were determined by HPLC or by fluorescence polarization immunoassay. Total body clearance (CL) and haemofilter clearance (CLf) rates were determined by standard model-independent equations. Data from published literature on fractions not bound to proteins (fu), non-renal drug clearance fractions (Qo), and normal clearance values (CLn) were used to derive a pharmacokinetic model, taking into account drug removal by ultrafiltration and by non-renal clearance. RESULTS: A total of 37 treatment periods was studied. Blood flow through the haemofilters was 100 ml/min resulting in an average ultrafiltrate flow rate (UFR) of 13.2 +/- 4.6 (range 3.2-22.1) ml/min. Acceptable correlations of calculated and measured haemofilter clearances and total body clearances were obtained. CONCLUSIONS: Total body clearance in anuric patients during CVVH is predictable from drug properties, which are generally known. The individual dosage requirements may be calculated by multiplying Qo + fu.UFR/CLn with the dose considered appropriate in the absence of renal impairment.

Acute Kidney Injury↗

Uremic small-artery disease with medial calcification and intimal hyperplasia (so-called calciphylaxis): a complication of chronic renal failure and benefit from parathyroidectomy.

BACKGROUND: Uremic small-artery disease with medial calcification and intimal hyperplasia can lead to life-threatening skin necrosis or acral gangrene. It is a distinct complication of chronic renal failure that must be differentiated from soft-tissue calcification. An increased calcium-phosphate product and secondary hyperparathyroidism are the main underlying conditions. The benefit of parathyroidectomy is controversial. OBJECTIVE: This article is based on a literature search to determine prognostic factors and, in particular, the benefit of parathyroidectomy. METHODS: The literature on uremic small-artery disease (so-called calciphylaxis) was reviewed (full data set: 104 cases, including five of our own). The therapeutic benefit of parathyroidectomy and the relation between prognostic predictors (localization, dialysis, and transplant) and outcome were analyzed. The relation between diabetes and acral gangrene was also examined. Further epidemiologic data on the reviewed group of patients were established. RESULTS: Thirty-eight of 58 patients who underwent parathyroidectomy survived compared with 13 of 37 patients who did not undergo parathyroidectomy (p = 0.007, n = 95). Forty of 53 patients with distal localization of necrosis survived compared with 11 of 42 patients with proximal pattern (p < 0.00001; n = 95). Dialysis and kidney transplantation followed by immunosuppression showed no relation to disease outcome. No association was found between diabetes and acral gangrene (p = 0.50). CONCLUSION: Uremic small-artery disease is a distinct complication of chronic renal failure. Its recognition and early diagnosis should allow more effective treatment. In our retrospective study parathyroidectomy was significantly related to survival. Only a randomized, controlled, prospective trial (parathyroidectomy vs conservative treatment of secondary hyperparathyroidism) can establish the value of parathyroidectomy in uremic small-artery disease.

Adult↗

[Hemolytic-uremic syndrome following kidney transplantation: prognostic factors].

Posttransplant hemolytic uremic syndrome (P-HUS) is a rare complication following kidney transplantation and is due to thrombotic microangiopathy. The aim of the present study was to determine patients at risk for this condition and to describe the follow-up in patients who developed P-HUS. The study is based on 557 consecutive patients who underwent either renal or combined renal and pancreatic transplantation in the cyclosporin era. P-HUS occurred in 19 out of 557 patients (3.4%). The reasons for developing P-HUS were: vascular rejection in 10 patients, association with cyclosporin in 5 patients, recurrence of an original HUS in 3 patients, and a transplanted shock-damaged kidney in 1 case. Patients with retransplants, grafts procured from non-heartbeating donors, high levels of anti-HLA antibodies, high HLA-DR mismatch, and HUS or Alport syndrome as the original disease, were found to be at increased risk for developing P-HUS. One-year graft survival for the P-HUS group was 42% and 88% for patients without this complication. Despite full therapy the prognosis of a P-HUS remains poor. Therefore, prevention of P-HUS, which consists in avoidance of the combination of the risk factors mentioned above, is emphasised.

Adult↗

[Long-term course following kidney transplantation].

The first 100 recipients of cadaveric renal allotransplants operated at our institution between 1964 and 1971 were retrospectively analyzed in terms of a long-term follow-up, complications and survival parameters. Patient and graft survival (indicated in parenthesis) after transplantation were 68% (58%) at 1 year, 50% (38%) at 5 years, 40% (27%) at 10 years, 32% (20%) at 15 years and 20% (13%) at 20 years. Half-life of graft survival was computed using two different mathematical models and was compared with the results of a control group operated in 1986. Half-life was 9.5 years for the study group and 13 years for the control group respectively.

Adolescent↗

Hepatitis C RNA prevalence in a Western European organ donor pool and virus transmission by organ transplantation.

Liver disease is a common finding after organ transplantation and might in part be due to transmission of hepatitis C virus (HCV). The aim of this study was to determine the prevalence of positive results with different anti-HCV tests and HCV-RNA in a local donor pool and to clarify to what extent HCV was transmitted to organ recipients. Serum samples from 207 consecutive organ donors were analysed retrospectively with anti-HCV ELISA (2nd and 3rd generation), anti-HCV RIBA (2nd generation) and HCV polymerase chain reaction (PCR). Organ recipients at risk were identified and followed up serologically and clinically. Anti-HCV seroprevalance in organ donors was 4.3% for 2nd generation ELISA, 4.8% for 3rd generation ELISA and 1.9% for 2nd generation RIBA. HCV-PCR was positive in 1.4%. Nine organs from four RIBA-positive donors were transplanted into eight recipients of whom four became anti-HCV and PCR positive after transplantation. HCV-PCR became positive several days after transplantation whereas anti-HCV seroconversion took place after 8-9 months. Two recipients developed acute liver disease and another two showed features of mild chronic liver disease but no serious complications due to HCV infection were observed.

Enzyme-Linked Immunosorbent Assay↗

Cytomegalovirus disease of late onset following renal transplantation: a potentially fatal entity.

CMV disease (CMVD) is a recognized problem of the early post-transplant period (PTP) in renal transplant recipients. Information on CMVD in the late (> or = 2 years) PTP is scarce. We have observed 5 cases of CMVD during late (3-8 years) PTP during the last 15 years. Three of these patients died from CMVD. One of the patients with late-onset CMVD recovered spontaneously from mild pneumonitis, 1 patient with severe CMVD after therapy with ganciclovir/anti-CMV-IgG. CMVD was ascribed to primary infection in 4/5 patients, and transmission was attributed to blood products in 2 cases. At the time of CMVD, 4/5 patients were on stable immunosuppression with azathioprine/prednisone; 1 patient who died had received prednisone pulses 1 month prior to CMVD. Late onset CMVD is an underreported disease in renal transplant recipients, which warrants preventive measures and consideration of antiviral therapy.

Adult↗

Pyrimethamine inhibits renal secretion of creatinine.

The mechanism of increased serum creatinine after administration of pyrimethamine and dapsone was evaluated for six healthy volunteers. Serum parameters, urine sediment, and clearances of creatinine, inulin, and para-aminohippurate were assessed prior to and 28 h after the ingestion of a single, combined dose of 100 mg of pyrimethamine and 200 mg of dapsone. In a second series, the same renal function tests were performed for nine human immunodeficiency virus-infected men before and after 1 month of prophylactic treatment with a weekly dose of 75 mg of pyrimethamine and 200 mg of dapsone to evaluate sustained effects on renal function. Serum creatinine increased within 28 h from 81 +/- 14 to 102 +/- 16 mumol/liter (P = 0.002) in the healthy volunteers. Blood urea nitrogen, beta 2-microglobulin, and urine remained normal. Creatinine clearance decreased from 125 +/- 27 to 91 +/- 26 ml/min (P < 0.02) without changes in inulin clearance. The effect was reversible within 21 days and attributable to pyrimethamine, as determined by administration of each drug alone. The sustained effect of four doses of pyrimethamine and dapsone in human immunodeficiency virus-infected patients consisted of an analogous rise in serum creatinine from 69 +/- 17 to 87 +/- 32 mumol/liter (P < 0.05). Both creatinine and inulin clearances, however, were unchanged, representing a new equilibrium between creatinine production and elimination at a higher level in serum. Pyrimethamine, thus, may reversibly inhibit renal tubular secretion of creatinine without affecting the glomerular filtration rate. This physiologic effect in pyrimethamine-treated patients must be differentiated from possible organ-related nephropathies.

Adult↗

IgA nephropathy and hypercalcemia in Whipple's disease.

In 2 patients an IgA nephropathy was found 2 and 5 years before gastrointestinal symptoms led to the diagnosis of Whipple's disease. One patient additionally presented with hypercalcemia. Subsequently 1 patient died, whereas treatment with trimethoprim/sulfamethoxazole resulted in an improvement of IgA nephropathy and in a complete recovery from hypercalcemia and all the manifestations of Whipple's disease in the other patient. IgA nephropathy and hypercalcemia may be considered as early manifestations of Whipple's disease.

Adult↗

[Drug side effects on the kidney].

That the kidneys are vulnerable to damage by drugs is due to functional and morphological factors. Nephrotoxic reactions due to drugs may affect each segment of the nephron, the medullary interstitium and the renal vasculature, resulting in different nephrotoxic syndromes. The drug-induced nephropathies of special clinical importance are reviewed and the most common nephrotoxic agents mentioned.

Drug Hypersensitivity↗

[The imaging diagnosis of sclerosing peritonitis (SP) following continuous ambulatory peritoneal dialysis (CAPD)].

Sclerosing peritonitis is a serious complication of CAPD characterised by thickened peritoneal membranes which lead to decreased ultrafiltration and intestinal obstruction. The roentgenographic signs of SP were analysed in 11 patients who underwent plain x-ray of the abdomen, follow-through examinations of the small bowel, ultrasonography and computed tomography. Results were correlated with the histological degree of SP. Besides the non-specific findings of intestinal obstruction, patients with histologically marked SP had loculated fluid collections, thickening of the bowel wall and/or peritoneum, peritoneal calcifications and thickened peritoneal membranes. Due to the fact that postoperative complications often occur in patients with SP, detection of the radiological signs should lead to cautious surgical interventions and changeover to haemodialysis.

Acute Disease↗

Performance characteristics of hemofilters with heparin surface coating: an experimental study.

Heparin surface coated hemofilters and tubing sets were evaluated in comparison to identical but uncoated controls in 8 bovine experiments (74+/-6 kg). No heparin was given (neither systemically nor in the priming fluid). The hemofilters were primed with one liter of Ringer's lactate in both groups and the maximal filter performance (arterial line pressure 300 mmHg; transmembrane pressure (TMP) 500 mmHg) was measured over 6 hours or until filter occlusion. All coated and one control filter remained functional during the scheduled 6 hours. The mean filter patency was 360+/-0 minutes for coated versus 210+/-99 minutes for uncoated (p less than 0.01). Mean blood flow at 1 hour and 6 hours was 675+/-114 and 580+/-96 ml/min for coated versus 432+/-183 and 25+/-43 for uncoated (NS; p less than 0.01). Mean filter output during the 6th hour and total filter output over 6 hours was 4225+/-998 ml and 21779+/-4273 for coated versus 400+/-692 and 7717+/-9757 for uncoated (p less than 0.01; p<0.01). Mean lactatedehydrogenase (LDH) levels before and 30 minutes after hemofiltration were 1855+/-411 IU and 2007+/-635 for coated versus 2160+/-411 and 1945+/-500 for uncoated (NS; NS). The heparin coated hemofilters demonstrated improved thromboresistance resulting in superior filter performance. There was no evidence of increased blood trauma.

Animals↗