Efficacy of plasma exchange in severe idiopathic rapidly progressive glomerulonephritis. A report of ten cases

The vast majority of patients with idiopathic rapidly progressive glomerulonephritis (RPGN) develop irreversible renal failure within weeks to months. We report a retrospective study of 10 patients with idiopathic RPGN who were treated with plasma exchange in addition to steroids and immunosuppression. Renal biopsies were obtained in nine patients. RPGN without immune complexes was present in four, immune complex disease in four, and anti-glomerular basement membrane disease in two. Renal function did not recover in those patients with anti-glomerular basement membrane disease. In contrast, seven of eight patients without auto-antibodies to basement membranes responded to therapy, and four did not need dialysis for two years or more. The sustained improvement in renal function in these seven patients suggests the need for evaluation of plasma exchange as an adjunct to steroids and immunosuppression in a prospective, controlled study in RPGN.     

The partial recovery of kidney function in chronic uremia patients during hemodialysis treatment

Out of 432 patients placed on the treatment with hemodialysis (HD) for terminal renal failure (TRF) at the All-Union Nephrologic Center from January 1, 1978 to December 31, 1987, 17 patients manifested partial recovery of renal function, which enabled dialysis treatment to be discontinued for a time. Among the 17 patients with noticeable improvement of renal function, 8 presented with lupoid rapid-progressing glomerulonephritis (RPGN), 2 with RPGN associated with hemorrhagic vasculitis, 1 with idiopathic RPGN, 4 with chronic glomerulonephritis (CGN), 1 with chronic pyelonephritis, and 1 with polycystic kidneys. In 11 patients with RPGN, the rate of renal failure progression, expressed by the regression coefficient, was much higher among those in whom HD treatment was discontinued that in the group of patients without renal function recovery. In the 4 patients with CGN, renal function was recovered after the correction of marked disorders of purine metabolism, whereas in the 1 patient with chronic pyelonephritis and in the 1 with polycystic kidneys after urinary infection elimination. According to the ultrasonography data, out of the 17 patients with partial recovery of renal function, the size of the kidneys turned out normal in 14 patients.     

急进性肾炎的诊治进展

急进性肾小球肾炎(rapidly progressive glomerulonephritis,RPGN)以急性肾炎综合征伴肾功能急剧恶化为临床特征,病理为新月体肾炎.早期诊断主要依靠血清免疫学检查及尽早肾活检.早期治疗应根据病理类型及患者情况采用个体化的治疗方案,包括强化治疗和免疫抑制治疗.     

Apheresis for MPO-ANCA-associated RPGN-indications and efficacy: lessons learned from Japan nationwide survey of RPGN

A national survey concerning rapidly progressive glomerulonephritis (RPGN) was conducted in Japan between 1989 and 2000 and resulted in the registration of 715 patients with RPGN. Among the documented patients, the most frequent primary disease was primary pauci-immune crescentic glomerulonephritis (n = 283), and the second most frequent was microscopic polyangitis (n = 127). Overall, 370 patients had MPO-ANCA, and 23 patients had PR3-ANCA. We found that both renal and patient survivals were significantly worse in patients with MPO-ANCA-associated RPGN than patients with PR3-ANCA. Fifty-three patients received apheresis therapy with various combinations of immunosuppressive regimens. They had higher serum creatinine, higher CRP, and a higher frequency of complicated pulmonary involvements as compared to the controls without apheresis therapy. In dialysis-dependent patients, no additional benefit from apheresis therapy was observed. Only pulmonary renal syndrome patients with CRP > 6 mg/dl at presentation showed a slightly better prognosis (patient survival with apheresis; 66.7%, without apheresis; 56.7%). Furthermore, a rapid MPO-ANCA titer reduction was observed in patients treated with apheresis. Patients with MPO-ANCA-associated RPGN were older, and had more chronic and sclerotic lesions than patients with PR3-ANCA-associated RPGN. Based on these findings, we suggest that a lower dose of immunosuppressant should be considered in order to avoid opportunistic infection. In this situation, cytapheresis is the treatment of choice. Nevertheless, in patients with an aggressive form of RPGN with rapid deterioration of renal function like the PR3-ANCA-associated RPGN, or pulmonary renal syndrome complicated severe inflammation, or relapses with high MPO-ANCA titer, we conclude that apheresis therapy should be considered.     

Cytapheresis for the treatment of myeloperoxidase antineutrophil cytoplasmic antibody-associated vasculitis: report of five cases.

To minimize the adverse effects of high-dose administration of steroids and cyclophosphamide in patients with myeloperoxidase (MPO) antineutrophil cytoplasmic antibody (ANCA), granulocytapheresis (GCAP) or leukocytapheresis (LCAP) was performed to reduce inflammation. Four patients with rapidly progressive glomerulonephritis (RPGN) and one patient with pulmonary hemorrhage due to MPO-ANCA-associated vasculitis were treated by cytapheresis. The prednisolone (PSL) dose was 0.28 +/- 0.15 mg/kg/day (mean +/- SD) (range 0.18-0.50 g/kg/day). In the 4 RPGN patients, the peak serum creatinine level was 3.7 +/- 1.9 mg/dl (range 1.7 to 5.6 mg/dl). GCAP was performed in 3 RPGN patients and in 1 pulmonary hemorrhage patient. LCAP was performed in 1 RPGN patient. In the 4 RPGN patients, renal function improved after combined therapy with cytapheresis and corticosteroids. In the pulmonary hemorrhage patient, evidence of pulmonary hemorrhage on chest computed tomography scanning diminished after combined therapy with cytapheresis and corticosteroids. Cytapheresis, when combined with a low-dose or intermediate-dose PSL regimen, is effective in the treatment of ANCA-associated vasculitis.     

Endocarditis-associated rapidly progressive glomerulonephritis mimicking vasculitis: a diagnostic and treatment challenge

BackgroundInfective endocarditis (IE)-associated rapidly progressive glomerulonephritis (RPGN) is rarely reported. Sporadic case reports have noted the diagnostic and therapeutic challenge in IE-associated glomerulonephritis because it may masquerade as idiopathic vasculitis.MethodsPatients with clinical diagnosis of IE-related RPGN in a tertiary hospital in China between January 2004 and May 2021 were identified and retrospectively reviewed.ResultsTwenty-four patients with IE-associated RPGN were identified. All patients presented with fever and multiorgan system involvement on top of heart and kidneys, spleen (79%, 19/24), skin (63%, 15/24), lung (33%, 8/24) and nervous system (17%, 4/24). Six of the 24 patients (25%) were initially suspected to have ANCA-associated or IgA vasculitis. Forty-five percent of patients are seropositive for ANCA. Renal histology showed mesangial and/or endocapillary hypercellularity with extensive crescents in most patients. C3-dominant deposition was the predominant pattern on immunofluorescence and pauci-immune necrotising crescentic glomerulonephritis was observed in one case. All patients received antibiotics with or without surgery. Six patients received immunosuppressive therapy before antibiotics due to misdiagnosis and seven patients received immunosuppressive therapy after antibiotics due to persistence of renal failure. Three of the 24 patients died due to severe infection. All the surviving patients had partial or complete recovery of renal function.ConclusionIE-associated RPGN is rare and the differential diagnosis from idiopathic vasculitis can be challenging due to overlaps in clinical manifestations, ANCA positivity and absence of typical presentations of IE. The prognosis is generally good if antibiotics and surgery are not delayed. The decision on introducing immunoruppressive treatment should be made carefully on a case by case basis when kidney function does not improve appropriately after proper anti-infective therapy.

Key messages

• Infective endocarditis associated RPGN is rare and differentiating it from idiopathic vasculitis can be challenging due to overlap in clinical manifestations, ANCA positivity and occasional absence of typical manifestations of infective endocarditis.
• Kidney function usually responds to antibiotic therapy alone.
• Immunosuppressive therapy may be beneficial in carefully selected patients whose kidney function does not improve with antibiotics alone.

     

Rapidly progressive glomerulonephritis in ANCA-associated vasculitis: a course, treatment efficacy, prognosis

AIM: To study efficacy of ANCA-RPGN treatment with corticosteroids and cyclophosphamide or mycophenolic acid drugs. MATERIAL AND METHODS: We treated 28 patients (17 males and 11 females aged 19-71 years) with morphologically verified ANCA-associated crescentic RPGN (crescentic median 79 (63:88)%. The patients received corticosteroids and cytostatics. RESULTS: The response to the treatment was registered in 22 (78%) patients in 8-16 weeks: a complete remission was achieved in 8 patients, a partial one--in 14 patients. In partial remission renal functions recovered incompletely (median Pcr 200 (180;255) mcmol/l) in persistence of moderate proteinuria (median 0.7 (0.6;1.3)g/day) and absence of microhematuria. Probability of the treatment success depended on severity of glomerulosclerosis and weakly depended on activity of extracapillary reaction. Severe renal failure was not an absolute predictor of treatment failure. CONCLUSION: In the absence of advanced nephrosclerosis early treatment with corticosteroid in combination with cytostatics can produce a positive effect in 70-80% patients with ANCA associated RPGN.     

Plasmapheresis in the treatment of rapidly progressive glomerulonephritis.

The present study was carried out to examine the efficacy of plasma exchange in patients with rapidly progressive glomerulonephritis (RPGN). Seventeen patients with RPGN were treated with plasmapheresis as adjunct to immunosuppressive therapy. Of these, 4 had antiglomerular basement membrane (GBM) antibody-mediated glomerulonephritis (GN), 8 had immune-complex GN (5 SLE, 2 HSP, 1 cryoblobulinemia), 5 had pauci-immune GN (3 peripheral antineutrophil cytoplasmic antibody [P-ANCA], 1 cytoplasmic antineutrophil cytoplasmic antibody [C-ANCA], 1 other). Treatment of 10 of these patients with plasmapheresis within the first month of disease onset resulted in a stable renal function for a period extending from 1 to 3 years, except in 2 patients who had high baseline levels of serum creatinine. In the remaining patients, 2 were treated with hemodialysis 6 years later at the end of follow-up. We conclude that plasmapheresis, when used in combination with immunosuppressive drugs, is beneficial, leading to improved renal function.     

Utilization of peritoneal dialysis in the acute setting.

Peritoneal dialysis (PD), although classically described and utilized in the treatment of patients with end-stage renal disease, can also be utilized in the acute setting in different clinical situations. Recent studies showed that, in patients with acute renal failure, it is possible to obtain reasonable dialysis doses with adequate metabolic and electrolytic control and low incidence of complications by utilizing continuous PD through a cycler at high volume. In patients with congestive heart failure without end-stage renal disease, PD is capable of promoting clinical improvement with slow removal of liquids, becoming an attractive alternative for situations of rapidly or slowly worsening cardiac function. In patients submitted to chronic hemodialysis but who have vascular access difficulties, PD can also be utilized as a "bridge," thereby avoiding the use of central venous catheters, which can be associated with infectious complications such as bacterial endocarditis. New studies must be realized showing other indications for PD.     

Hepatorenal failure

Renal failure in patients with liver disease is a common finding and may arise by a number of different mechanisms. However, in patients with cirrhosis or fulminant hepatic failure renal failure is often said to be functional. The urinary sodium concentration is low and the urine osmolality often high. This syndrome is also called hepatorenal failure. Recent studies, however, have indicated a range of renal function from functional at one end to acute tubular necrosis at the other. Functional renal failure seems to have a circulatory basis within the kidney holding out hope that, in theory at least, it might be possible to reverse it by pharmacological manipulation. In the meantime, a trial of dialysis in a series of patients with liver disease who developed renal failure has shown that if improvement of liver function can be expected, or if there is a clear precipitating cause for renal failure, then treatment of renal failure should be vigorous and expectant.     

Diabetic nephropathy--recent therapeutic concepts

Optimal metabolic control, strict antihypertensive therapy and a low-protein diet may reduce renal functional disorders such as hyperfiltration and microalbuminuria in the initial and latent phase of diabetic nephropathy and may retard progression of renal functional loss in the clinically-manifest proteinuric, azotaemic phase. Increasing clinical experience with renal replacement therapy in the end-stage renal failure of diabetic nephropathy led to a worldwide rise in the percentage of diabetic patients in dialysis centres. However, full rehabilitation is not achieved and retinopathy may progress to complete blindness. As a result of better rehabilitation and possible stabilisation of diabetic neuropathy and retinopathy after renal transplantation, in diabetic patients a kidney graft should be available early in the course of progressing renal failure.     

A rapidly progressing variant of subacute infectious endocarditis

A total of 122 patients with subacute infectious endocarditis (SIE) were examined. Of these, 33 patients demonstrated an extremely severe disease course. In spite of adequate antibacterial treatment, the lethal outcome ensued within the first 2-2.5 years of the disease. A rapidly progressing variant of SIE was characterized by persistent fever, predominance of aortal heart diseases, renal injuries with an early development of renal failure, hemorrhagic vasculitis, relapsing thromboembolism, refractory heart failure, persistent anemia, lymphopenia, and by the presence of large movable vegetations discovered on echocardiography.     

Assessing recovery of renal function after tenofovir disoproxil fumarate discontinuation

Impaired renal function caused by tenofovir disoproxil fumarate (TDF) is considered reversible by discontinuing TDF administration, but there are occasional cases of incomplete recovery. We investigated the recovery of renal function after the discontinuation of TDF. Subjects comprised patients who had been started on TDF but in whom it was later discontinued because of impaired renal function. We investigated renal function until 96 weeks after the discontinuation of TDF, and the duration of TDF administration, up to May 2010. TDF was discontinued because of impaired renal function in 21 of 766 patients (2.7%). Following discontinuation, a significant recovery was seen in eGFR (p = 0.003). The median duration of administration was 28 days (6-941 days) in 9 patients whose eGFR recovered to pre-administration levels, 405 days (250-1,379) in 7 patients in whom mild recovery was seen, and 1,110 days (421-1,470) in 5 patients in whom eGFR was much lower than at the time of discontinuation. A significant correlation was seen between the eGFR recovery rate and the duration of TDF administration. TDF administration was discontinued because of renal impairment in 2.7% of patients. The duration of TDF administration was short in patients whose renal function recovered to pre-administration levels, but patients in whom sufficient recovery was not seen after discontinuation had received TDF over long periods and included many whose renal function gradually declined, even after discontinuation. Recovery of renal function after discontinuation of TDF is likely affected by the duration of TDF administration.     

Plasmapheresis for crescentic IgA nephropathy: a report of two cases and review of the literature

Idiopathic IgA nephropathy is widely regarded as a slowly progressive disease that not infrequently results in end-stage renal failure. Only a minority of patients present with either a rapidly progressive form of glomerulonephritis, or with end-stage renal failure. Anecdotal reports of improved renal function after treatment with plasmapheresis have been published, but the efficacy of this therapy remains controversial. We describe the course of two young males presenting with uremia, hypertension, nephrotic-range proteinuria, and crescentic glomerulonephritis on renal biopsy. Both patients underwent therapy with steroids, immunosuppressive agents, and plasmapheresis without an appreciable improvement in renal function. A review of the literature does not offer any conclusive data to support the role of plasmapheresis in the treatment of rapidly progressive glomerulonephritis due to IgA nephropathy and points out the need to define criteria that may identify subsets of patients with this disorder who may potentially benefit from plasma exchange therapy. J. Clin. Apheresis 14:185-187, 1999. Published 1999 Wiley-Liss, Inc.     

多发性骨髓瘤合并肾功能损害的诊断及治疗

肾功能损害(RI)是多发性骨髓瘤(MM)的常见并发症.初诊MM患者中,20％～40％的患者系MM合并中、重度RI,＞10％的MM患者合并肾功能衰竭,并且需要接受血液透析治疗.改善肾功能、及时进行抗MM治疗,对MM合并RI患者的预后具有非常重要的临床意义.近年来,MM合并RI的诊断及治疗均取得重大进展.笔者就MM合并RI的诊断、评估及治疗现状进行综述,并对目前MM合并RI的抗MM治疗方案进行比较.     

Recovery of renal function and the discontinuation of dialysis in patients treated with continuous peritoneal dialysis.

OBJECTIVE: Previous studies have shown that patients with end-stage renal disease (ESRD) treated with continuous peritoneal dialysis (CPD) have better preservation of endogenous renal function than patients treated with hemodialysis (HD). We wondered if this better preservation of endogenous renal function seen with CPD patients translates into the improved likelihood of recovery of endogenous renal function in those patients with potentially reversible causes of renal failure. METHODS: To evaluate this question, we reviewed the records of all 1200 patients that completed CPD training at a large, freestanding peritoneal dialysis center in New Haven, Connecticut, between 1979 and 1999, and the records of all patients completing CPD training in New England between 1993 and 1998. In New Haven, about half the new patients with ESRD were started on CPD compared to only 15% in New England. We then compared the chances of recovery of renal function in these two cohorts of CPD patients to the chances of recovery of renal function in two groups of HD patients. The first group consisted of all patients that started on HD in New England between 1993 and 1998.The second group consisted of all patients that started HD in our HD unit in New Haven, Connecticut, between 1993 and 1999. The data on the New England patients were provided by the ESRD Network of New England. All patients entered into the present study had to have been on dialysis for a minimum of 3 months, as in the United States Renal Data System database, and had to have recovered sufficient renal function to be able to be maintained off dialysis for a minimum of 30 days. RESULTS: 29 of 1,200 CPD patients (2.4%) trained in New Haven recovered sufficient renal function to permit the discontinuation of dialysis for a minimum of 30 days. In comparison, only 305 of 19,032 patients (1.6%) managed with HD in New England (p < 0.05 compared to New Haven CPD patients) and 3 of 430 patients (0.7%) in our HD center (p < 0.05 compared to New Haven CPD patients) recovered sufficient glomerular filtration rate (GFR) to allow the discontinuation of dialysis for at least 30 days. If only those CPD patients that initiated dialysis between 1993 and 1999 in New Haven were analyzed, 15 of 369 (4.1%) recovered sufficient GFR to allow discontinuation of dialysis for at least 30 days (p < 0.025 compared to both groups of HD patients). Of the 2,924 patients completing CPD training in New England, 60 (2.1%) recovered renal function; this percentage is not significantly different from the percent of HD patients in New England recovering renal function. CONCLUSION: Although the present study is a retrospective study and the actual criteria for selection of CPD and HD therapy are not controlled for, the data raise the question of whether there may be a therapeutic advantage to treating newly diagnosed ESRD patients, that have a potentially reversible cause of renal failure, with CPD.     

Clinical and morphological aspects of the management of crescentic anti-glomerular basement membrane antibody (anti-GBM) nephritis/Goodpasture's syndrome

Twenty-two patients with crescentic anti-GBM nephritis or Goodpasture's syndrome with renal impairment were reviewed. All patients were treated with a combination of plasma exchange and immunosuppression. Sixteen patients (73 per cent) showed improvement in renal function (greater than 30 per cent reduction in serum creatinine level) apparently in response to treatment, and nine patients (41 per cent) made long-term recoveries in renal function. The most important features carrying a bad prognosis were total anuria, and/or a very high percentage of glomeruli showing crescents (greater than 85 per cent) in the initial renal biopsy. Some patients with other so-called 'bad' prognostic features, including severely impaired renal function at presentation, oliguria and the need to institute dialysis had unexpected marked improvement in renal function and/or recovered renal function in the long term provided treatment with plasma exchange was begun promptly and maintained for a sufficient period to allow resolution of the disease process. Renal biopsies at the beginning and later proved to be an extremely valuable guide for the progress and outcome of the disease.     

Zoledronic Acid and renal toxicity: data from French adverse effect reporting database

BACKGROUND: Zoledronic acid-associated renal impairment leading to renal failure has been recently reported in a cohort of US patients. However, the presence of such toxicity in other populations has not yet been determined. OBJECTIVE: To analyze French cases of zoledronic acid-associated nephrotoxicity. METHODS: We evaluated available cases with acute deterioration of renal function associated with zoledronic acid therapy drawn from the French Adverse Event Reporting System database until July 1, 2004. RESULTS: We identified 4 men and 3 women between the ages of 52 and 70 years, with multiple myeloma or different types of metastatic cancer, who had experienced renal impairment during zoledronic acid therapy. Four patients developed de novo acute renal failure, while the other 3 patients experienced acute deterioration of preexisting chronic renal failure. Renal failure occurred after various durations of zoledronic acid therapy (1-120 days). Three patients completely recovered and one partially recovered their previous renal function after discontinuation of zoledronic acid, but renal impairment was associated with a fatal outcome in 2 cases; the outcome of the other case was unknown. Our data confirm the previously reported risk factors for zoledronic acid-associated nephrotoxicity such as advanced cancer, multiple myeloma, preexisting renal failure, diabetes, hypertension, and concomitant use of nephrotoxic drugs. CONCLUSIONS: These cases emphasize the need for regular monitoring of renal function during zoledronic acid treatment, with particular attention to patients with preexisting impaired renal function.     

Continuous hemodiafiltration with polymyxin-B immobilized fiber is effective in patients with sepsis syndrome and acute renal failure.

The aim of this study was first, to evaluate the effects of continuous hemodiafiltration (CHDF) alone or combined with CHDF and polymyxin-B immobilized fiber (PMX) on survival rates of patients with sepsis and acute renal failure, and second, to evaluate the changes in plasma levels of inflammatory cytokines before and after treatment with CHDF and PMX and CHDF alone in these patients. Forty-eight patients with septic shock and acute renal failure were enrolled in this study. The survival rate of all patients at 28 days was 25% for those with CHDF and 75% for those with PMX and CHDF treatment. Combination treatment produced a significant reduction of plasma levels of endotoxin and interleukin-6 compared to the basal values and to the treatment with CHDF alone. From these data, it is suggested that the combined therapy with PMX and CHDF is effective in improvement of survival rate of patients with septic shock and acute renal failure.