Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0035078 (renal failure)
 31,970 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have recently described hereditary membranoproliferative glomerulonephritis type II in the pig. All affected animals had excessive complement activation, revealed as low plasma C3, elevated plasma terminal complement complex, and massive deposits of complement in the renal glomeruli, and eventually died of renal failure within 11 wk of birth. The aim of the present study was to investigate the cause of complement activation in this disease. Transfusion of normal porcine plasma to affected piglets inhibited complement activation and increased survival. Plasma was successively fractionated and the complement inhibitory effect of each fraction tested in vivo. A single chain 150-kD protein which showed the same complement inhibitory effect as whole plasma was finally isolated. Immunologic cross-reactivity, functional properties, and NH2-terminal sequence identified the protein as factor H. By Western blotting and enzyme immunoassay, membranoproliferative glomerulonephritis-affected piglets were demonstrated to be subtotally deficient in factor H. At 1 wk of age, median (range) factor H concentration was 1.6 mg/liter (1.1-2.3) in deficient animals (n = 13) and 51 mg/liter (26-98) in healthy littermates (n = 52). Our data show that hereditary porcine membrano-proliferative glomerulonephritis type II is caused by factor H deficiency.
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PMID:Hereditary porcine membranoproliferative glomerulonephritis type II is caused by factor H deficiency. 788 53

Pigs genetically deficient in complement factor H all develop lethal membranoproliferative glomerulonephritis (MPGN) type II characterized by massive glomerular deposits of complement, intramembranous dense deposits, and mesangial hypercellularity. To elucidate the chronological relationship between these glomerular changes, and to precisely determine the localization of glomerular complement deposits, we studied kidney specimens from factor H-deficient piglets at different ages from fetal life until terminal kidney failure had developed. Deposits of C3 and the terminal complement complex localized within the glomerular basement membrane (GBM) were present already in factor H-deficient fetuses, without concurrent intramembranous dense deposits or mesangial hypercellularity. Incipient subendothelial dense deposits containing complement appeared no earlier than four days after birth, and intramembranous dense deposits in older piglets with established MPGN type II also contained large amounts of complement as detected by immune electron microscopy. Onset of kidney failure coincided with pronounced mesangial hypercellularity and expansion, compromising glomerular capillary patency. Formation of glomerular capillary wall double contours coincided with electron microscopic evidence of laminar disintegration of intramembranous dense deposits. Complement was also deposited in the mesangial matrix, but not on glomerular cells. We conclude that all components of the alternative and terminal pathways of complement have access into the GBM and the mesangial matrix. In the absence of factor H, complement is spontaneously activated and deposited in situ in these locations resulting in dense deposit formation. It is proposed that factor H dysfunction may play an essential role even in human MPGN type II.
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PMID:In situ complement activation in porcine membranoproliferative glomerulonephritis type II. 946 Oct 93

A patient with homozygous factor H deficiency presented with hemolytic uremic syndrome (HUS) at the age of 7 months. After a 2-year period of stability, renal failure and erythrocyte fragmentation recurred between the age of 3 and 4 years. Fresh frozen plasma infusions allowed renal function to be improved and erythrocyte fragmentation to be stopped. Withdrawal of plasma therapy led to a relapse of the biological signs of HUS.
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PMID:Successful plasma therapy in hemolytic uremic syndrome with factor H deficiency. 1146 3

The term thrombotic microangiopathy (TMA) encompasses syndromes of thrombocytopenia, microangiopathic haemolytic anaemia, neurologic deficits, renal dysfunction and variable signs of organ impairment. Childhood cases of TMA with predominant renal failure are usually referred as Haemolytic Uremic Syndrome (HUS), and adult cases with major neurological involvement as Thrombotic Thrombocytopenic Purpura (TTP). Exotoxins, produced in most cases by E. Coli O 157:H7, have been related to diarrhea associated HUS(D + HUS). Anticancer (mitomycin), immunosuppressive drugs (cyclosporin, tacrolimus and OKT3) and as well as some antiplatelet agents (ticlopidine, clopidrogel) have been associated with both HUS and TTP. Defective factor H or vWF protease activity have been found with familiar and recurrent forms. Endothelial damage and dysfunction is most likely the initial event of the pathogenic process that eventually leads to platelet aggregation, microvascular thrombosis and tissue ischemia. TMA may occur de novo in the native kidneys of patients who received a non-kidney transplant or in the transplanted kidney of patients who progressed to ESRD because of a disease other than HUS. Calcineurin inhibitors and vascular rejection are most often involved in these cases. The disease may also recur on the transplanted kidney in patients who progressed to ESRD because of HUS/TTP. The risk of postransplant recurrence is negligible for D + HUS but is close to 100% in familial/recurrent forms associated with low C3 and decreased factor H bioavailability or activity. Withdrawal or treatment of precipitating factors are the most effective approach. Plasma therapy is usually attempted with the rationale to limit the microangiopathic process, but its efficacy for improving graft survival is unproven. The outcome of recurrent forms is almost invariably poor.
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PMID:Thrombotic microangiopathy in renal transplantation. 1222 1

Atypical hemolytic uremic syndrome (HUS) frequently leads to end-stage renal failure and can relapse after transplantation. A 12-year-old girl presenting with familial atypical HUS with a factor H mutation was successfully transplanted 6 years after a first transplant that had failed because of immediate recurrent HUS. Prophylactic plasma exchange before and after transplantation was used. Two months after transplantation, concomitant with a reduction in plasma exchange frequency, the plasma creatinine increased from 70 micro mol/l to 194 micro mol/l in 2 weeks without thrombocytopenia or signs of hemolytic anemia. The patient had minimal clinical symptoms and a presumptive diagnosis of graft rejection was made. Despite treatment with six daily pulses of methylprednisolone, plasma creatinine continued to increase and a graft biopsy was therefore undertaken. This showed the typical appearance of a thrombotic microangiopathy without any evidence of rejection. Despite daily plasmapheresis and replacement of cyclosporine with tacrolimus, there was no improvement and transplant nephrectomy was undertaken. This patient demonstrates that HUS can recur in a kidney transplant without the diagnostic hematological features and emphasizes the need for early transplant biopsy in such patients showing a decline in transplant function.
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PMID:Atypical relapse of hemolytic uremic syndrome after transplantation. 1530 Apr 78

Quantitative or functional deficiency of complement factor H results in uncontrolled complement activation. This leads to thrombotic microangiopathy and finally causes renal failure (atypical hemolytic uremic syndrome [aHUS]). By regular analysis of factor H in patients with aHUS, the authors found a complete factor H deficiency in an infant in whom aHUS developed at 8 months of age. Factor H was quantified by enzyme-linked immunosorbent assay and further analyzed by Western blot using a factor H-specific antibody. Complement activation was determined by measuring total hemolytic activity of the classical (CH50) and alternative (APH50) pathways, C3 and C3d. The sequence of factor H gene was determined. Serial factor H measurements after fresh frozen plasma infusion allowed calculation of a factor H half-life. Factor H was absent in plasma (<1 mug/mL), and the complement system was highly activated (CH50, APH50, C3 decreased; C3d increased). Genetic analysis identified a novel homozygous factor H mutation (T2770A; Y899Stop) in CCP domain 15, most likely causing defective protein secretion. Time course measurements of factor H after plasma infusion established a factor H half-life of about 6 days. By repetitive plasma infusions (20 mL/kg over about 2 to 3 hours) the authors were able to interrupt the vicious circle of thrombotic microangiopathy in a factor H-deficient patient with aHUS. Based on the measured factor H half-life of about 6 days, regular plasma infusions in 2-week intervals were given, which prevented further aHUS episodes and stopped the decline of kidney function.
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PMID:Successful plasma therapy for atypical hemolytic uremic syndrome caused by factor H deficiency owing to a novel mutation in the complement cofactor protein domain 15. 1568 22

Atypical hemolytic uremic syndrome (HUS) can recur after renal transplantation and often leads to graft loss. In some series of familial HUS, the risk of early graft loss due to recurrence of HUS approaches 100% despite any therapy. This led some authors to claim that kidney transplantation is contraindicated in those patients. The authors describe an 8-year-old girl with end-stage renal failure owing to familial atypical HUS with a factor H mutation who underwent successful transplantation using continuous prophylactic plasma exchange (PE). Twenty-four months after transplantation, plasma creatinine level is 1.2 mg/dL (106 micromol/L) despite 2 recurrences of HUS contemporaneous to 2 cytomegalovirus infections, which resolved with PE intensification and ganciclovir. This strongly suggests that cytomegalovirus infection may trigger posttransplant recurrent HUS. The feasibility of kidney transplantation in case of atypical HUS related to factor H mutation using continuous prophylactic PE intensified during relapses should be confirmed in prospective studies.
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PMID:Posttransplantation cytomegalovirus-induced recurrence of atypical hemolytic uremic syndrome associated with a factor H mutation: successful treatment with intensive plasma exchanges and ganciclovir. 1569 34

Membranoproliferative glomerulonephritis type II (MPGN II) is a rare disease characterized by the deposition of abnormal electron-dense material within the glomerular basement membrane of the kidney and often within Bruch's membrane in the eye. The diagnosis is made in most patients between the ages of 5 and 15 yr, and within 10 yr, approximately half progress to end-stage renal disease, occasionally with the late comorbidity of visual impairment. The pathophysiologic basis of MPGN II is associated with the uncontrolled systemic activation of the alternative pathway (AP) of the complement cascade. In most patients, loss of complement regulation is caused by C3 nephritic factor, an autoantibody directed against the C3 convertase of the AP, but in some patients, mutations in the factor H gene have been identified. For the latter patients, plasma replacement therapy prevents renal failure, but for the majority of patients, there is no proven effective treatment. The disease recurs in virtually all renal allografts, and a high percentage of these ultimately fail. The development of molecular diagnostic tools and new therapies directed at controlling the AP of the complement cascade either locally in the kidney or at the systemic level may lead to effective treatments for MPGN II.
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PMID:Membranoproliferative glomerulonephritis type II (dense deposit disease): an update. 1580 Jan 16

HEMOLYTIC UREMIC SYNDROME POST-PARTUM: We describe a case of a 37-year-old woman admitted for severe renal failure to our hospital immediately after the delivery by caesarean section of twins. She had anuria, anemia, and moderate thrombocytopenia. A diagnosis of hemolytic-uremic syndrome was made. Plasma exchange was started, substitution was performed with fresh frozen plasma and eight consecutive plasmapheresis sessions were given. She received hydrocortisone and ACE inhibitors. After about fifteen days from the beginning of the illness, signs of active haemolysis disappeared and renal function was partially recovered. A genetic study demonstrated the absence of HF1 and MCP mutations but a polymorphic variant of the HF1 gene (C-257T promoter region). This polymorphism is strongly associated with non-diarrhoea-HUS (D-HUS). Post-partum HUS is quite a rare syndrome and has a poor outcome; however prompt diagnosis and efficacious therapy could save lives without clinical consequences. The excellent outcome of this patient seems to corroborate this concept.
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PMID:A post-partum hemolytic-uremic-like-syndrome in a patient with pre-eclampsia: description of a clinical case. 1642 9

Hemolytic uremic syndrome not associated with diarrhea (diarrhea negative, atypical) is less common than the diarrhea-positive typical form, but frequently results in end-stage renal failure. Although there are anecdotal cases of successful treatment with fresh frozen plasma alone, the value of this treatment compared with plasma exchange (PE) is difficult to assess. We describe monozygotic female twins who presented at 5 years of age with factor H-related (c.3572 > T; Ser1191Leu) atypical hemolytic uremic syndrome within months of each other. In the first twin to present, 10 sessions of PE with fresh frozen plasma replacement (40 mL/kg) resulted in resolution of hemolysis and improvement in plasma creatinine level (1.9 to 1.5 mg/dL [166 to 137 micromol/L]). Subsequently, 17 infusions of fresh frozen plasma were administered during a 4-month period for recurrent thrombocytopenia. However, within 4 months, plasma creatinine level increased to 5.1 mg/dL (450 micromol/L), necessitating peritoneal dialysis. When the second twin presented with the same disease, an extended PE regimen was instituted. After 10 daily sessions, PE was continued once every 2 weeks. Two recurrences were treated successfully with daily PE for 7 days. After 44 months of follow-up, kidney function is normal (plasma creatinine, 0.6 mg/dL [53 micromol/L]; creatinine clearance, 119 mL/min/1.73 m2 [1.98 mL/s/1.73 m2]) on maintenance PE therapy. In conclusion, the response to treatment of these monozygotic twins suggests that long-term PE may have benefits over plasma infusion alone.
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PMID:Complement factor H-associated atypical hemolytic uremic syndrome in monozygotic twins: concordant presentation, discordant response to treatment. 1643 Dec 47


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