Monogenic Kidney Diseases in Kidney Transplantation.

Monogenic kidney diseases are involved in up to 15% of end-stage kidney diseases (ESKDs) in adults, and in 70 % of pediatric patients. When these disorders lead to kidney failure (KF), kidney transplantation (KT) is the preferred mode of replacement therapy. KT requires specific considerations depending on the nature of the genetic disorder, the potential oncological risk, the risk of recurrence in the graft, the possibility of specific complications of immunosuppression, and the issue of living donation. The availability of genetic testing should play an increasing role in the evaluation of patients or related living donor candidates before transplantation, relevant for the pretransplantation and posttransplantation management.

Refining Kidney Survival in 383 Genetically Characterized Patients With Nephronophthisis.

Introduction: Nephronophthisis (NPH) comprises a group of rare disorders accounting for up to 10% of end-stage kidney disease (ESKD) in children. Prediction of kidney prognosis poses a major challenge. We assessed differences in kidney survival, impact of variant type, and the association of clinical characteristics with declining kidney function. Methods: Data was obtained from 3 independent sources, namely the network for early onset cystic kidney diseases clinical registry (n = 105), an online survey sent out to the European Reference Network for Rare Kidney Diseases (n = 60), and a literature search (n = 218). Results: A total of 383 individuals were available for analysis: 116 NPHP1, 101 NPHP3, 81 NPHP4 and 85 NPHP11/TMEM67 patients. Kidney survival differed between the 4 cohorts with a highly variable median age at onset of ESKD as follows: NPHP3, 4.0 years (interquartile range 0.3-12.0); NPHP1, 13.5 years (interquartile range 10.5-16.5); NPHP4, 16.0 years (interquartile range 11.0-25.0); and NPHP11/TMEM67, 19.0 years (interquartile range 8.7-28.0). Kidney survival was significantly associated with the underlying variant type for NPHP1, NPHP3, and NPHP4. Multivariate analysis for the NPHP1 cohort revealed growth retardation (hazard ratio 3.5) and angiotensin-converting enzyme inhibitor (ACEI) treatment (hazard ratio 2.8) as 2 independent factors associated with an earlier onset of ESKD, whereas arterial hypertension was linked to an accelerated glomerular filtration rate (GFR) decline. Conclusion: The presented data will enable clinicians to better estimate kidney prognosis of distinct patients with NPH and thereby allow personalized counseling.

Severe hypercalcaemia early after kidney transplantation in two patients with severe secondary hyperparathyroidism previously treated with etelcalcetide.

Cinacalcet and, more recently, etelcalcetide revolutionized the treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). Kidney transplant (KT) usually improves CKD-MBD. However, a significant proportion of KT recipients have high serum calcium levels, not requiring any treatment. We report two patients previously treated with etelcalcetide who developed severe (>3.3 mmol/L) hypercalcaemia in the early post-KT course, requiring parathyroidectomy. Pathological studies showed parathyroid adenomas and hyperplasia. One patient had a graft biopsy showing numerous intratubular calcium phosphate crystals. These observations should prompt pharmacovigilance studies and careful follow-up of KT recipients previously treated with etelcalcetide.

Recurrence and Outcome of Anti-Glomerular Basement Membrane Glomerulonephritis After Kidney Transplantation.

INTRODUCTION: Recurrence of anti-glomerular basement membrane (anti-GBM) glomerulonephritis in the kidney graft is a rare event, described in limited reports. The aim of this study was to evaluate, in a large cohort of patients with long follow-up, the risk of recurrence of anti-GBM disease, the risk factors associated with clinical recurrence, and the long-term patient and graft survival. METHODS: This was a multicenter retrospective study. Inclusion criteria were patients with anti-GBM glomerulonephritis who underwent transplantation of a kidney between 1977 and 2015. Exclusion criteria were systemic vasculitis, lupus erythematosus, and cryoglobulinemia. Recurrence was defined as reappearance of clinical signs of glomerulonephritis along with histological signs of proliferative glomerulonephritis and linear IgG staining on kidney biopsy, with or without anti-GBM antibodies. RESULTS: A total of 53 patients were included. Recurrence of anti-GBM glomerulonephritis in a first kidney transplant occurred in only 1 patient 5 years after transplantation (a prevalence rate of 1.9%) in the context of cessation of immunosuppressive drugs, and resulted in graft loss due to recurrence. Linear IgG staining on kidney biopsy in the absence of histological signs of proliferative glomerulonephritis was observed in 4 patients, in the context of cellular rejection. Patient survival was 100%, 94%, and 89% at 5, 10, and 15 years, respectively. Death-censored first-graft survival rates were 88%, 83%, and 79% at 5, 10, and 15 years, respectively. CONCLUSION: The recurrence rate of anti-GBM glomerulonephritis after transplantation is very low but is associated with graft loss. The long-term patient and graft survival rates are excellent.

Extremely rapid stone formation in cystinuria: look out for dietary supplements!

Cystinuria is an autosomal recessive disease characterized by recurrent nephrolithiasis. The prevention of new stones is based on diluting and alkalinizing urine, as well as a low salt and moderate protein intake. The avoidance of food rich in methionine (the precursor of cystine) is also advocated. We report the case of a young adult adherent to the preventative strategy who was stone-free and within months formed a large stone. This coincided with the recent intake of a dietary supplement containing both cystine and methionine. Patients and physicians should be aware of the potential harm of such supplements in patients with cystinuria.

Rhabdomyolysis and acute kidney injury induced by the association of rosuvastatin and abiraterone: A case report and review of the literature.

INTRODUCTION: Abiraterone acetate is an inhibitor of androgens biosynthesis, approved as first-line treatment in castration-resistant prostate cancer and metastatic castration-sensitive prostate cancer. Abiraterone has been rarely associated with severe rhabdomyolysis, but the mechanism of muscle toxicity is unknown. CASE REPORT: We hereby present a case of severe rhabdomyolysis resulting in acute on chronic kidney injury following abiraterone initiation in a patient previously under rosuvastatin. MANAGEMENT AND OUTCOME: Rhabdomyolysis was resolutive after rosuvastatin and abiraterone discontinuation, and kidney function recovered. There was no recurrence of muscle toxicity after re-initiation of abiraterone alone. DISCUSSION: Abiraterone selectively inhibits CYP17 as well as the hepatic transporter OATP1B1. OATP1B1 is an efflux transporter, whose function is to extract several drugs from the portal blood, allowing them to undergo hepatic metabolism. We hypothesize that abiraterone-induced inhibition of plasmatic uptake of rosuvastatin by OATP1B1 increased plasmatic concentration of rosuvastatin, leading to toxicity on muscle cells. We therefore suggest that the association between rosuvastatin and abiraterone should be avoided.

Cystinuria: clinical practice recommendation.

Cystinuria (OMIM 220100) is an autosomal recessive hereditary disorder in which high urinary cystine excretion leads to the formation of cystine stones because of the low solubility of cystine at normal urinary pH. We developed clinical practice recommendation for diagnosis, surgical and medical treatment, and follow-up of patients with cystinuria. Elaboration of these clinical practice recommendations spanned from June 2018 to December 2019 with a consensus conference in January 2019. Selected topic areas were chosen by the co-chairs of the conference. Working groups focusing on specific topics were formed. Group members performed systematic literature review using MEDLINE, drafted the statements, and discussed them. They included geneticists, medical biochemists, pediatric and adult nephrologists, pediatric and adult urologists experts in cystinuria, and the Metabolic Nephropathy Joint Working Group of the European Reference Network for Rare Kidney Diseases (ERKNet) and eUROGEN members. Overall 20 statements were produced to provide guidance on diagnosis, genetic analysis, imaging techniques, surgical treatment (indication and modalities), conservative treatment (hydration, dietetic, alkalinization, and cystine-binding drugs), follow-up, self-monitoring, complications (renal failure and hypertension), and impact on quality of life. Because of the rarity of the disease and the poor level of evidence in the literature, these statements could not be graded. This clinical practice recommendation provides guidance on all aspects of the management of both adults and children with cystinuria, including diagnosis, surgery, and medical treatment.

Etiologies, Clinical Features, and Outcome of Oxalate Nephropathy.

BACKGROUND: Oxalate nephropathy is a potentially underestimated cause of kidney failure characterized by massive deposition of calcium oxalate crystals in the renal parenchyma. The prevalence and modes of presentation of this entity are ill-defined. METHODS: Here we report on the largest consecutive series of cases of adult oxalate nephropathy diagnosed on native kidney biopsies from January 2010 to December 2018 in the UCLouvain Kidney Disease Network. RESULTS: We screened 2265 native kidney biopsies and identified 22 cases (1%) of oxalate nephropathy. Patients had a mean age at diagnosis of 61 years (±20) and presented either with acute on chronic kidney disease (CKD) (62%) or with acute kidney injury (AKI) (38%). Mean serum creatinine at biopsy was 8.0 ± 4.5 mg/dl. Kidney biopsies showed abundant calcium oxalate crystal deposits, associated with acute interstitial nephritis and tubular necrosis, and variable degrees of interstitial fibrosis and tubular atrophy. Chronic pancreatitis and gastric bypass were the most common causes of oxalate nephropathy (48%). During a mean follow-up of 29 months, half of the patients (52%) progressed to kidney failure, all within the month following diagnosis. Higher serum creatinine level at presentation and interstitial fibrosis and tubular atrophy score were associated with progression to kidney failure. CONCLUSION: Oxalate nephropathy is the cause of kidney disease in 1% of consecutive native kidney biopsies and typically presents as acute on CKD or AKI. The prognosis of the disease is poor, with a high rate of kidney failure within the first month after the diagnosis.

ANCA vasculitis in a patient with Alport syndrome: a difficult diagnosis but a treatable disease!

BACKGROUND: Alport syndrome and ANCA-associated vasculitis are both rare diseases. The co-existence of these two conditions has never been reported. There is no obvious pathogenic link between these two glomerular diseases. The management of this case highlights the importance of a systematic approach when investigating the unexpected unfavourable evolution of a known glomerulopathy. CASE PRESENTATION: A-17 year old caucasian boy with a genetically proven X-linked Alport syndrome presented with progressive dyspnea, fatigue and pallor. His blood tests showed a severe anemia (Hb 6.9 g/dl) with acute worsening of kidney function (serum creatinine, normal 9 months earlier, was now 3.6 mg/dl). Microscopic hematuria and proteinuria also worsened. He soon developed signs of alveolar hemorrhage. Serological tests showed the presence of perinuclear ANCA with anti MPO specificity. Kidney biopsy showed a necrotizing and crescentic glomerulonephritis. Pulses of methylprednisolone were given in combination with plasmapheresis. The patient further received 6 pulses of cyclophosphamide, followed by maintenance oral azathioprine. During the 15-months follow up he remained well with serum creatinine back to normal, and some residual proteinuria and hematuria ascribed to Alport syndrome. CONCLUSION: We report a young patient with the coexistence of Alport syndrome and ANCA associated vasculitis. Clinicians should be aware of the possibility of a second acquired disease in a patient with a known kidney disease, genetic in this case. This coexistence is very rare, but should be considered even if both diseases are rare, if the evolution is atypical for the single (known) primary disease. The diagnosis of the added vasculitis prompted in our case the initiation of immunosuppressive drugs, with a favourable outcome.