Monoallelic Loss-of-Function IFT140 Pathogenic Variants Cause Autosomal Dominant Polycystic Kidney Disease: A Confirmatory Study With Suspicion of an Additional Cardiac Phenotype.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease. While biallelic variants affecting IFT140 are responsible for Mainzer-Saldino syndrome (characterized by severe ciliopathy causing skeletal abnormalities, kidney disease, and cysts), monoallelic loss-of-function (LoF) variants have been recently reported as an important cause of ADPKD beyond PKD1/2 genes. Herein, we report 6 non-family-related cases of monoallelic IFT140 LoF variants, identified from 1,340 exomes sequenced for nephrological indications in our local database. Every patient presented with polycystic kidney disease. Furthermore, the mother of a boy diagnosed with Mainzer-Saldino syndrome with a biallelic variant affecting IFT140 presented with several bilateral cysts, revealed after kidney imaging, and was found to carry a pathologic frameshift IFT140 variation. As well as this particular Mainzer-Saldino case, our 6 additional patients confirm that heterozygous IFT140 frameshift variants are responsible for the cystic phenotype and kidney failure. Interestingly, of the 6 patients, 2 also exhibited dilated cardiomyopathy, which was of unknown origin, as no genetic cause was found after exome sequencing analysis, suggesting a potential connection between IFT140 and heart disease.

A severe oxaliplatin immune-induced syndrome after oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy (PIPAC).

Objectives: Oxaliplatin immune-induced syndrome (OIIS) was recently recognized as an uncommon complication of oxaliplatin therapy. Methods: We report an exceptionally OIIS after pressurized intraperitoneal aerosol chemotherapy (PIPAC). Results: Our patient developed a severe OIIS probably related to the intraperitoneal administration of oxaliplatin. Specific tests were performed and detected high-titer antibodies to oxaliplatin. Conclusions: The OIIS is a rare. Physicians had to be aware of that clinical situation because it could be reversible, even in case of peritoneal advanced disease, and ICU treatment is justified.

Predictive factors of glomerular filtration rate loss associated with living kidney donation: a single-center retrospective study.

PURPOSE: Living kidney donors (LKD) partially compensate the initial loss of glomerular filtration rate (GFR), a phenomenon known as renal functional reserve (RFR). RFR is reduced in the elderly, a population with increased prevalence of chronic kidney disease. We hypothesized that the selected, healthy population of LKD, would specifically inform about the physiological determinants of the RFR and studied it using measured GFR (mGFR). METHODS: We retrospectively analyzed pre-donation and post-donation mGFR in 76 LKD from Tenon Hospital (Paris, France) between 2002 and 2018. In addition to GFR measurements, we collected pre-donation morphologic parameters, demographic data, and kidney volumes. RESULTS: Mean pre-donation mGFR was 90.11 ± 12.64 mL/min/1.73 m2 and decreased to 61.26 ± 9.57 mL/min/1.73 m2 1 year after donation. Pre-donation mGFR correlated with age (p = 0.0003), total kidney volume (p = 0.0004) and pre-donation serum creatinine (p = 0.0453). Pre-donation mGFR strongly predicted 1-year post-donation mGFR. Mean RFR (increase in GFR of the remnant kidney between pre-donation and post-donation) was 36.67 ± 16.67% 1 year after donation. In the multivariate linear model, RFR was negatively correlated to total kidney volume (p = 0.02) but not with age or pre-donation serum creatinine. CONCLUSIONS: We found that pre-donation mGFR decreases with age and identified low total kidney volume as a predictor of RFR in healthy individuals. This suggests an adaptative and reversible decrease in kidney function rather than age-related damage. Older subjects may have reduced metabolic requirements with subsequent reduction in glomerular filtration and kidney volume and preserved RFR. Therefore, low GFR in older subjects should not preclude kidney donation.

Retinal Arteriolar Occlusions and Exudative Retinal Detachments in Malignant Hypertension: More Than Meets the Eye.

BACKGROUND: Malignant hypertension is macrovascular and microvascular endothelial injury responsible for multiple organ damage. Considering the anatomical and functional homologies between the posterior pole of the eye and the kidney, ophthalmological explorations may inform clinicians on the mechanisms underpinning concurrent kidney injury in this condition. More specifically, we investigated whether the wall-to-lumen ratio (WLR) of retinal arterioles measured by adaptive optics ophthalmoscopy could be correlated to WLR of kidney arterioles as determined by pathology. We sought to estimate the incidence of retinal arteriole occlusion a supposedly uncommon complication of malignant hypertension. METHODS: All patients hospitalized in our renal Intensive Care Unit for malignant hypertension between 2016 and 2019 were referred to ophthalmological examinations. RESULTS: Twenty-seven patients were included. Median retinal WLR was 0.39 [0.31-0.47] and was correlated with initial systolic (r = 0.56, P = 0.003) and mean blood pressure (r = 0.46, P = 0.02) upon admission. The retinal WLR was not correlated to renal pathological findings, as assessed by juxtaglomerular WLR (r = 0.38, P = 0.2), ratio of glomerulosclerosis (r = -0.39, P = 0.2), or tubulointerstitial fibrosis (r = -0.45, P = 0.08). Retinal WLR was not associated with neurological or cardiovascular end-organ damage. Branch retinal artery occlusion was detected in 18.5% of patients and exudative retinal detachment (ERD) in 29.6% of patients, without any significant correlation with canonical signs of retinal hypertension including optic disc swelling. CONCLUSIONS: In the setting of malignant hypertension, we failed to demonstrate a significant relationship between WLR and other meaningful end-organ injuries. However, branch retinal artery occlusion and ERD may have been hitherto underestimated.