Treatment of the renal involvement in mixed cryoglobulinemia with prolonged plasma exchange

Nine patients with mixed cryoglobulinemia and severe membranoproliferative glomerulonephritis were treated with plasma exchange alone or in combination with medium to low amounts of corticosteroids, but never with cytotoxic drugs. In 5 patients renal function and/or proteinuria improved after plasma exchange, and no clinical relapse usually occurred when the procedures were reduced or discontinued. These procedures seemed of particular effect in the presence of histologically active and not irreversible lesions and rapid deterioration of renal function. While cryocrit almost invariably decreased, circulating immune complex or complement levels were unpredictably affected by plasma exchange. Cryocrit, but not immune complex or complement levels, was the serological parameter which most often closely correlated with signs of renal involvement (i.e., proteinuria and/or serum creatinine). Thus, plasma exchange might be a safe and useful tool in the treatment of an often drug-resistant and rapidly progressive renal involvement occurring in patients with mixed cryoglobulinemia.     

Successful treatment of acute renal failure in a patient with essential mixed cryoglobulinemia using prednisolone and cryofiltration

We report a case of acute renal failure associated with cryoglobulinemic glomerulonephritis. The patient, a 49-year-old woman, was referred to our hospital because of acute nephritic syndrome. After admission, she developed oliguria, and hemodialysis was instituted. Renal biopsy was performed and the specimens showed moderate endocapillary proliferation, large deposits filling the capillary lumen ("intraluminal thrombi"), and a double-contoured appearance, which are typical morphologic features of cryoglobulinemic glomerulonephritis. Immunoelectrophoresis showed a monoclonal increase of IgM kappa. On the basis of these findings, we diagnosed type II essential mixed cryoglobulinemia. Cryofiltration was performed with oral administration of prednisolone. Following the start of therapy, the patient's renal function gradually improved. Because of severe hypoproteinemia, cryofiltration was discontinued after three sessions. However, renal function recovered and was maintained with prednisolone only. This case shows that acute oliguric renal failure caused by cryoglobulinemic glomerulonephritis can be reversible if immunosuppressive therapy, together with plasmapheresis in more severe cases, is instituted promptly.     

Renal involvement in essential mixed cryoglobulinemia

Essential mixed cryoglobulinemia (EMC) is infrequently recognized in this country. We report studies performed in six patients with EMC evaluated by us over the last 6 years. Purpura was present in three patients and glomerulonephritis in all. Two patients had chronic hepatitis B infection. Positive cryoglobulins and C1q binding, hypocomplementemia (especially low C4), positive rheumatoid factor titer, and negative anti-DNA antibodies were characteristic laboratory findings. The cryoprecipitate had strongly positive rheumatoid factor activity and contained a monoclonal IgM, kappa type in one of the two patients evaluated. The predominant lesion by renal biopsy was mesangiocapillary glomerulonephritis type I; electron microscopy revealed typical fibrillar structures in four cases. The above-mentioned features help distinguish EMC from other forms of glomerulonephritis.     

Intravenous methylprednisolone pulse therapy in essential mixed cryoglobulinemia nephropathy

In 15 patients with essential mixed cryoglobulinemia, 24 exacerbations of renal disease, characterized by an increase in plasma creatinine (13 episodes) and/or proteinuria (18 episodes), were treated by 3 intravenous pulses of methylprednisolone (1 g each), followed by oral prednisone (0.5 mg/kg/day). Plasma creatinine levels fell within a week (P less than 0.025), while a significant decrease in urinary protein excretion was observed only after one month (P less than 0.05). After therapy, plasma creatinine levels remained stable in 8/10 patients for 3 to 60 months. These beneficial results suggest that MP pulses may be useful in the treatment of cryoglobulinemic nephropathy.     

Acute renal failure in dense deposit disease: complete recovery after combination therapy with immunosuppressant and plasma exchange

We describe the clinical course of a female adolescent who was followed because of isolated microhematuria and hypocomplementemia before admission to hospital with a sudden onset of acute renal failure. At presentation, she exhibited complement consumption through the complement alternative pathway (AP) while other serologic tests were negative. Renal biopsy revealed dense deposit disease (DDD) with a crescentic pattern. Intravenous methylprednisolone, followed by plasma exchange (PE), and intravenous cyclophosphamide pulses were started shortly after admission. C3NeF and anti-factor H antibody tests were negative. Serum factor H and I levels were normal as well as factor H activity. Screening for mutation in the factor H gene revealed the H402 allele variant. Clinical remission, defined as normalization in renal function and in the activity levels of the complement AP, was noted at one month post-presentation and throughout the follow-up. A repeat renal biopsy showed the disappearance of crescent formation, whereas electron microscopy revealed no regression in dense transformation of the lamina densa. In summary, our patient was successfully treated with immunosuppressant and PE. The absence of known factors associated with DDD suggests that, in this particular case, other regulatory mechanisms of complement AP might have been involved in the disease process.     

Acute renal failure with preserved renal plasma flow induced by cancer immunotherapy

Adoptive immunotherapy in patients with advanced cancer produces significant regression of metastatic disease in selected patients, but it is complicated by severe side effects. Prevention of these complications is still limited because their precise mechanisms remain unknown. For this reason we have investigated renal function and hemodynamic parameters in 16 patients with renal cell carcinoma before and during treatment with a combination of high doses of both recombinant interleukin-2 (rIL2) and recombinant alpha-interferon. After patients had received three injections of combined immunotherapy, there was a decrease in mean blood pressure (-20%), glomerular filtration rate (-25%), urine output (-50%), and fractional sodium excretion (-0.8%). This was associated with an increase in heart rate (+30%), plasma creatinine level (+30%), fractional potassium excretion (+14%) and microalbuminuria (+130%). However, renal plasma flow remained constant. The increment in microalbuminuria may reflect an alteration of glomerular capillary permeability. The reduction in GFR may be accounted either for a decrease in efferent to afferent arteriolar resistance ratio, leading to a decrease in glomerular capillary pressure, or for a decrease in ultrafiltration coefficient, or both. Nonsteroidal antiinflammatory drugs, such as ketoprofen, used to minimize side effects, could considerably worsen renal function and should be avoided in patients treated by rIL2. Our results bring new insights into the pathogenesis of functional acute renal failure and provide a rational basis for the use of vasopressors in the treatment of cytokine-induced acute renal failure.     

Recurrent essential mixed cryoglobulinemia in renal allografts. Report of two cases and review of the literature

This report describes two patients in whom essential IgG-IgM mixed cryoglobulinemia (EMC) glomerulonephritis led to end-stage renal disease. Both patients underwent primary hemodialysis, and during the period of uremia clinical and biological manifestations of the disease fully resolved. Transplantation was performed, and in both cases cryoglobulinemia quickly recurred (30 days and 6 months after transplantation, respectively) with clinical renal and extrarenal flare, and reappearance of the biological markers of the disease (decrease in C3 and C4 components of serum complement, detection of rheumatoid activity and of cryoglobulinemia in the serum). The literature on EMC glomerulonephritis leading to end-stage renal disease is reviewed. Factors that may have contributed to extinguishing the disease and to further recurrence following transplantation-consequences of uremic state, alloimmunization and intercurrent infectious disease-are discussed.     

Plasmapheresis as sole therapy in a patient with essential mixed cryoglobulinemia

An 82-year-old woman with essential mixed cryoglobulinemia type II (IgM K IgG) presented with moderate renal failure and nephritic syndrome. Mesangiocapillary glomerulonephritis with mesangial and subendothelial granular deposits containing IgG, IgM, and C3 in conjunction with small-vessel vasculitis was seen on renal biopsy. Renal symptomatology preceded by a period of 10 months the development of leg ulcers and purpura. The onset of the skin lesions was accompanied by an acute decline of renal function and an increase in liver alkaline phosphatase. Plasmapheresis with a 50% plasma exchange each week over 12 weeks led to improvement in renal function, healing of leg ulcerations, disappearance of purpura, and a return to the baseline of alkaline phosphatase in association with the disappearance of circulating cryoglobulins.     

Rituximab therapy for mixed cryoglobulinemia in seven renal transplant patients

Systemic B-cell depletion and clinical remission of the systemic effects of cryoglobulins have been achieved in hepatitis C virus-positive immunocompetent patients with rituximab, a human/mouse chimeric monoclonal antibody that specifically reacts with the CD20 antigen. Thus, this provides a rationale for the use of rituximab for type III cryoglobulin-related graft dysfunction in renal-transplant patients. Seven patients, of whom five were hepatitis C positive, developed renal function impairment long after transplantation, as well as de novo nephrotic syndrome (n = 5), severe hypertension (n = 5), nephritic syndrome (n = 1), and increased serum creatinine (n = 1). This type III cryoglobulinemia was associated with membranoproliferative glomerulonephritis and with thrombi within the glomeruli in one case. In addition to their baseline standard immunosuppressive medications, the patients were given weekly rituximab infusions: 375 mg/m(2) for 2 weeks in four cases, for 3 weeks in one case, and for 4 weeks in two cases. This treatment resulted in a dramatic improvement in all renal parameters, particularly a sustained remission of nephrotic syndrome in three cases, the disappearance of nephritic syndrome in one patient, and improved nephrotic syndrome in two cases, as well as a sustained clearance of cryoglobulins in six cases. However, it also resulted in severe infectious complications in two cases. We concluded that rituximab therapy is effective in cryoglobulin-related renal dysfunction in renal transplant patients but, due to chronic immunosuppression, this may be achieved at the expense of infectious complications.     

Acute renal failure: Update

Canadian Journal of Anesthesia/Journal canadien d'anesthésie -     

Rituximab therapy for de novo mixed cryoglobulinemia in renal transplant patients

BACKGROUND: Type II or III cryoglobulins are fairly prevalent in renal-transplant (RT) patients, and are often related to chronic hepatitis C virus (HCV) infection. However, they rarely result in graft dysfunction. They are sustained by proliferation of oligoclonal B-cells. Systemic B-cell depletion and clinical remission of the systemic effects of cryoglobulins have been achieved in HCV-positive immunocompetent patients with a human/mouse chimeric monoclonal antibody that specifically reacts with the CD20 antigen (i.e., rituximab). Thus, this provides the rationale to use rituximab for cryoglobulin-related graft dysfunction in RT patients. METHODS: Three RT patients, of whom one was HCV-positive, developed renal-function impairment long after transplantation, as well as de novo nephrotic syndrome (n=2) and severe hypertension (n=2). This latter case was related to type III cryoglobulinemia and was associated with membranoproliferative glomerulonephritis. In addition to their baseline standard immunosuppression, the patients were given weekly rituximab infusions of 375 mg/m (two infusions in patient and four infusions for the other two cases). RESULTS: This treatment resulted in a dramatic improvement in renal parameters, particularly in a sustained remittence of nephrotic syndrome, a sustained clearance of cryoglobulins in two cases, but also in severe infectious complications in two cases. CONCLUSION: We conclude that rituximab therapy is highly effective in cryoglobulin-related renal dysfunction in RT patients; however, due to chronic immunosuppression, this is at the expense of infectious complications.     

Controlled plasma exchange trial in acute renal failure due to multiple myeloma

We studied 29 patients affected by acute renal failure due to multiple myeloma with Bence-Jones proteinuria greater than 1 g/day to evaluate the effectiveness of plasma exchange in the treatment of severe myeloma nephropathy. Renal failure was severe enough to require dialysis in 24 cases, while the remaining 5 patients showed serum creatinine levels greater than 5 mg/dl. The patients were randomly allocated to Group I (15 patients undergoing plasma exchange together with corticosteroids, cytotoxic drug, hemodialysis only when needed) or to Group II (14 patients undergoing peritoneal dialysis together with corticosteroids and cytotoxic drug). In Group I Bence-Jones proteinuria decreased dramatically (P less than 0.01) with a significant increase in urine output (P less than 0.001), while Group II presented a slight reduction in Bence-Jones proteinuria without a significant increase in daily diuresis. Thirteen out the 15 Group I patients recovered renal function reaching serum creatinine levels less than or equal to 2.5 mg/dl in most cases. Only two patients in Group II improved renal failure well enough to stop dialysis. The one-year survival rate was significantly higher in Group I (66%) than in Group II (28%, P less than 0.01). We conclude that plasma exchange associated to chemotherapy rapidly removes large amounts of light chains, improves both renal function and long-term survival expectancies.     

Acute renal failure induced by foscarnet: 4 cases

Foscarnet (FC) is a new antiviral agent which has been recently proposed for the treatment of severe cytomegalovirus (CMV) infections in immunocompromised patients. When used intravenously (i.v.), main adverse effects of FC are a fall in hemoglobin, and an increase in liver enzymes and serum calcium. Although increased serum creatinine have been noted in several patients, deterioration of renal function is often accounted for by the concomitant use of other nephrotoxic drugs, the severity of underlying disease or the presence of graft rejection. Consequently FC is often considered as a non or poorly nephrotoxic drug. We report 4 cases of acute renal failure (ARF) which can be exclusively attributed to FC. FC was used for CMV chorioretinitis in 3 AIDS patients and in one non-immunocompromised patient. ARF was diagnosed between the 6th and 15th day of treatment, with oligoanuria in two patients (one of whom required two hemodialysis periods). ARF was most likely secondary to acute toxic tubulopathy. Three patients did not receive any other nephrotoxic drug. The fourth patient received concomitantly sulfadiazine but renal function returned to baseline value after FC completion although sulfadiazine was continued. In conclusion, our 4 observations suggest that FC may be responsible for acute tubulopathy. We suggest that in these patients renal function should be carefully monitored and dehydration promptly corrected to limit the risk of nephrotoxicity.     

Acute renal failure in pregnancy: 1987

Acute renal failure has become a rare complication of pregnancy due to the virtual disappearance of septic abortion and to better prenatal care, including prevention of blood volume contraction. The incidence of bilateral renal cortical necrosis also decreased in recent years. Severe preeclampsia-eclampsia may be accompanied by acute tubular necrosis. Acute fatty liver of pregnancy is often associated with renal failure. It is a medical emergency. The diagnosis should be made promptly, before liver failure becomes too severe. This should be followed by immediate delivery. In postpartum hemolytic uremic syndrome, plasma infusion, plasma exchange, and/or antiplatelet drug therapy may be of value.