Neutrophil:lymphocyte ratio predicts short-term outcome of COVID-19 in haemodialysis patients.

BACKGROUND: Information regarding coronavirus disease 2019 (COVID-19) in haemodialysis (HD) patients is limited and early studies suggest a poor outcome. We aimed to identify clinical and biological markers associated with severe forms of COVID-19 in HD patients. METHODS: We conducted a prospective, observational and multicentric study. Sixty-two consecutive adult HD patients with confirmed COVID-19 from four dialysis facilities in Paris, France, from 19 March to 19 May 2020 were included.Blood tests were performed before diagnosis and at Days 7 and 14 after diagnosis. Severe forms of COVID-19 were defined as requiring oxygen therapy, admission in an intensive care unit or death. Cox regression models were used to compute adjusted hazard ratios (aHRs). Kaplan-Meier curves and log-rank tests were used for survival analysis. RESULTS: Twenty-eight patients (45%) displayed severe forms of COVID-19. Compared with non-severe forms, these patients had more fever (93% versus 56%, P < 0.01), cough (71% versus 38%, P = 0.02) and dyspnoea (43% versus 6%, P < 0.01) at diagnosis. At Day 7 post-diagnosis, neutrophil counts, neutrophil:lymphocyte (N:L) ratio, C-reactive protein, ferritin, fibrinogen and lactate dehydrogenase levels were significantly higher in severe COVID-19 patients. Multivariate analysis revealed an N:L ratio >3.7 was the major marker associated with severe forms, with an aHR of 4.28 (95% confidence interval 1.52-12.0; P = 0.006). After a median follow-up time of 48 days (range 27-61), six patients with severe forms died (10%). CONCLUSIONS: HD patients are at increased risk of severe forms of COVID-19. An elevated N:L ratio at Day 7 was highly associated with the severe forms. Assessing the N:L ratio could inform clinicians for early treatment decisions.

Prospective comparison of the use of sirolimus and cyclosporine in recipients of a kidney from an expanded criteria donor.

A 6-month, open-label, multicenter prospective pilot study was conducted to evaluate the effects of sirolimus (SRL) versus cyclosporine (CsA) in recipients of kidneys from expanded criteria donors. All patients also received antithymocyte globulins induction, mycophenolate mofetil, and steroids. Sixty-nine patients (33 SRL, 36 CsA) were randomized. More patient were withdrawn in the SRL group (16 vs. 6, P<0.01), because of delayed graft function and surgical complications. Delayed graft function tended to be more frequent with SRL than with CsA (45.4% vs. 30.6%, P=0.22). Graft survival was numerically lower in the SRL group (87.5% vs. 97%, P=0.19). At 6 months, there were no significant differences in biopsy-proven acute rejection or calculated creatinine clearance (SRL 12.1% vs. CsA 8.3%; P=0.7 and 44.7+/-16.6 vs. 41.9+/-15.2 mL/min; P=0.54 respectively). These results do not support the use of SRL immediately after transplantation in expanded criteria donor recipients.

Presentation and outcome of patients with systemic amyloidosis undergoing dialysis.

BACKGROUND AND OBJECTIVES: Light chain (AL) and secondary (AA) amyloidosis usually present as a systemic disease frequently involving the kidney and leading to ESRD. Data regarding patients with AA or AL amyloidosis undergoing dialysis remain scarce. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We retrospectively studied patients with AA or AL amyloidosis who started dialysis in five French centers between January 1, 1995 and December 31, 2005. RESULTS: We identified 19 patients with AL and 20 patients with AA amyloidosis undergoing dialysis. Patients with AL amyloidosis had shorter time from diagnosis to dialysis (25.2 versus 69.3 mo, P < 0.05) and more extrarenal amyloidosis, especially cardiac (63.2 versus 5%, P < 0.0001). Mean duration of follow-up was 37.4 and 31.8 mo for patients with AL and AA amyloidosis, respectively. Fifteen patients (78.9%) with AL and three patients (15%) with AA amyloidosis died on dialysis. Median survival was shorter in patients with AL (26 mo) than AA amyloidosis [not definable (ND)] (P < 0.02). Sepsis and cardiac deaths were the main causes of mortality. Prognosis factors for death at 1 yr were AL type (P < 0.01), cardiac amyloidosis [odds ratio (OR) = 18, P < 0.01], heart failure (OR = 8, P < 0.04), and shorter time from diagnosis to dialysis (6.1 versus 56 mo, P < 0.03). Multivariate analysis indicated that AL type (P = 0.02), but not cardiac amyloidosis was independently associated with global mortality. CONCLUSIONS: Survival of patients with amyloidosis undergoing dialysis, especially AL type, is probably better than previously reported. However, mortality is higher in AL than AA type, especially in the setting of cardiac involvement.

A cluster of mutations in the UMOD gene causes familial juvenile hyperuricemic nephropathy with abnormal expression of uromodulin.

Familial juvenile hyperuricemic nephropathy (FJHN [MIM 162000]) is an autosomal-dominant disorder characterized by abnormal tubular handling of urate and late development of chronic interstitial nephritis leading to progressive renal failure. A locus for FJHN was previously identified on chromosome 16p12 close to the MCKD2 locus, which is responsible for a variety of autosomal-dominant medullary cystic kidney disease (MCKD2). UMOD, the gene encoding the Tamm-Horsfall/uromodulin protein, maps within the FJHN/MCKD2 critical region. Mutations in UMOD were recently reported in nine families with FJHN/MCKD2 disease. A mutation in UMOD has been identified in 11 FJHN families (10 missense and one in-frame deletion)-10 of which are novel-clustering in the highly conserved exon 4. The consequences of UMOD mutations on uromodulin expression were investigated in urine samples and renal biopsies from nine patients in four families. There was a markedly increased expression of uromodulin in a cluster of tubule profiles, suggesting an accumulation of the protein in tubular cells. Consistent with this observation, urinary excretion of wild-type uromodulin was significantly decreased. The latter findings were not observed in patients with FJHN without UMOD mutations. In conclusion, this study points to a mutation clustering in exon 4 of UMOD as a major genetic defect in FJHN. Mutations in UMOD may critically affect the function of uromodulin, resulting in abnormal accumulation within tubular cells and reduced urinary excretion.

Combined dipyridamole-exercise stress echocardiography for detection of myocardial ischemia in hemodialysis patients: an alternative to stress nuclear imaging.

BACKGROUND: Stress nuclear imaging is the noninvasive technique currently used to detect coronary artery disease (CAD) in dialysis patients. Stress echocardiography is recognized as an alternative to stress nuclear imaging for the general population. The aim of this study is to assess the diagnostic accuracy of stress echocardiography for detecting myocardial ischemia in hemodialysis patients. METHODS: Stress echocardiography and stress technetium-99m-tetrofosmin (Myoview; Amersham International Plc) imaging were performed simultaneously for 66 asymptomatic hemodialysis patients in a single session, using a combination of high-dose dipyridamole and symptom-limited exercise. Coronary angiography was performed in 44 patients with at least one abnormal noninvasive test result or who were considered high-risk despite normal noninvasive test results. RESULTS: Results for stress echocardiography were abnormal in 15 patients (22%); stress Myoview, in 14 patients (21%); and coronary angiography, in 12 patients (18%). The sensitivity of stress echocardiography for detecting myocardial ischemia (defined as stress Myoview defect) was 86%; specificity, 94%; positive predictive value, 80%; negative predictive value, 96%; and overall accuracy, 92%. The sensitivity of stress echocardiography for detecting CAD (defined as abnormal coronary angiography result) was 83%; specificity, 84%; positive predictive value, 67%; negative predictive value, 93%; and overall accuracy, 84%. Stress echocardiography and stress Myoview did not differ significantly in overall accuracy for detecting CAD (84% versus 91%; P = not significant). CONCLUSION: In hemodialysis patients, combined dipyridamole-exercise echocardiography is an accurate method to detect both myocardial ischemia and CAD and represents an alternative to stress nuclear imaging.

[Antibodies against human recombinant erythropoietin: an unusual cause of erythropoietin resistance]. / Anticorps anti-érythropoïétine humaine recombinante: une cause exceptionnelle de résistance à l'érythropoïétine.

In a 70 year old man with primary glomerulonephritis, severe anemia occurred after 4 years on hemodialysis and rHu-EPO. The usual mechanisms of EPO-resistance were excluded. A bone marrow sample showed red all aplasia. No circulating EPO could be detected; the serum inhibited the growth of erythroid precursors in bone marrow cultures. Immunoprecipitation identified an IgG anti-EPO, still active against deglycosylated EPO, i.e. directed against the peptidic matrix. Its high neutralising capacity and the absence of any immune abnormality rule out an auto-antibody. Anti-rHu EPO immunisation is a very rare occurrence, made severe by transfusion-dependence and the risk of hemosiderosis. An immuno-modulating treatment can therefore be justified.

Pure red-cell aplasia and antierythropoietin antibodies in patients treated with recombinant erythropoietin.

BACKGROUND: Within a period of three years, we identified 13 patients in whom pure red-cell aplasia developed during treatment with recombinant human erythropoietin (epoetin). We investigated whether there was an immunologic basis for the anemia in these patients. METHODS: Serum samples from the 13 patients with pure red-cell aplasia were tested for neutralizing antibodies that could inhibit erythroid-colony formation by normal bone marrow cells in vitro. The presence of antierythropoietin antibodies was identified by means of binding assays with the use of radiolabeled intact, deglycosylated, or denatured epoetin. RESULTS: Serum from all 13 patients blocked the formation of erythroid colonies by normal bone marrow cells. The inhibition was reversed by epoetin. Antibodies from 12 of the 13 patients bound only conformational epitopes in the protein moiety of epoetin; serum from the remaining patient bound to both conformational and linear epitopes in erythropoietin. In all the patients, the antibody titer slowly decreased after the discontinuation of treatment with epoetin. CONCLUSIONS: Neutralizing antierythropoietin antibodies and pure red-cell aplasia can develop in patients with the anemia of chronic renal failure during treatment with epoetin.