Kaliopenic nephropathy revisited

Elitok, Saban; Bieringer, Markus; Schneider, Wolfgang; Luft, Friedrich C.

doi:10.1093/ckj/sfv154

Cited by 8 publications

(7 citation statements)

References 15 publications

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“…This view is supported by renal histopathological findings in BS, which are initially normal except for hyperplasia of the juxtaglomerular apparatus and glomerular atrophy [ 21 ]. Importantly, this contrasts with chronic kaliopenic nephropathy by laxative abuse, which is characterized by vacuolar changes in renal tubular epithelium accompanied by inflammatory interstitial changes in patients with potassium losses [ 22 ]. Therefore, Walsh et al suggested that long-term blockade of the mineralocorticoid receptor in BS with spironolactone or eplerenone (or perhaps even be direct renin inhibition) may be justified more for renal protection than for trying to correct hypokalaemia per se .…”

Section: Discussionmentioning

confidence: 99%

Late-onset Bartter syndrome type II

Gollasch

Anistan

Canaan–Kühl

et al. 2017

Clinical Kidney Journal

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Mutations in the ROMK1 potassium channel gene (KCNJ1) cause antenatal/neonatal Bartter syndrome type II (aBS II), a renal disorder that begins in utero, accounting for the polyhydramnios and premature delivery that is typical in affected infants, who develop massive renal salt wasting, hypokalaemic metabolic alkalosis, secondary hyperreninaemic hyperaldosteronism, hypercalciuria and nephrocalcinosis. This BS type is believed to represent a disorder of the infancy, but not in adulthood. We herein describe a female patient with a remarkably late-onset and mild clinical manifestation of BS II with compound heterozygous KCNJ1 missense mutations, consisting of a novel c.197T > A (p.I66N) and a previously reported c.875G > A (p.R292Q) KCNJ1 mutation. We implemented and evaluated the performance of two different bioinformatics-based approaches of targeted massively parallel sequencing [next generation sequencing (NGS)] in defining the molecular diagnosis. Our results demonstrate that aBS II may be suspected in patients with a late-onset phenotype. Our experimental approach of NGS-based mutation screening combined with Sanger sequencing proved to be a reliable molecular approach for defining the clinical diagnosis in our patient, and results in important differential diagnostic and therapeutic implications for patients with BS. Our results could have a significant impact on the diagnosis and methodological approaches of genetic testing in other patients with clinical unclassified phenotypes of nephrocalcinosis and congenital renal electrolyte abnormalities.

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Section: Discussionmentioning

confidence: 99%

Late-onset Bartter syndrome type II

Gollasch

Anistan

Canaan–Kühl

et al. 2017

Clinical Kidney Journal

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“…(C) Loss of potassium through RAAS activation and/or tubular injury may have secondary effects on renal blood flow. Long-term potassium depletion may lead to tubulointerstitial inflammation, a condition called hypokalemic or kaliopenic nephropathy [ 85 , 86 ]. Although this condition is not well studied in humans [ 85 , 86 ], it is related to vasoconstriction and impaired angiogenesis in rodents [ 87 ].…”

Section: The Theoretical Frameworkmentioning

confidence: 99%

Pathophysiological Mechanisms by which Heat Stress Potentially Induces Kidney Inflammation and Chronic Kidney Disease in Sugarcane Workers

et al. 2020

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Background: Chronic kidney disease of non-traditional origin (CKDnt) is common among Mesoamerican sugarcane workers. Recurrent heat stress and dehydration is a leading hypothesis. Evidence indicate a key role of inflammation. Methods: Starting in sports and heat pathophysiology literature, we develop a theoretical framework of how strenuous work in heat could induce kidney inflammation. We describe the release of pro-inflammatory substances from a leaky gut and/or injured muscle, alone or in combination with tubular fructose and uric acid, aggravation by reduced renal blood flow and increased tubular metabolic demands. Then, we analyze longitudinal data from >800 sugarcane cutters followed across harvest and review the CKDnt literature to assess empirical support of the theoretical framework. Results: Inflammation (CRP elevation and fever) and hyperuricemia was tightly linked to kidney injury. Rehydrating with sugary liquids and NSAID intake increased the risk of kidney injury, whereas electrolyte solution consumption was protective. Hypokalemia and hypomagnesemia were associated with kidney injury. Discussion: Heat stress, muscle injury, reduced renal blood flow and fructose metabolism may induce kidney inflammation, the successful resolution of which may be impaired by daily repeating pro-inflammatory triggers. We outline further descriptive, experimental and intervention studies addressing the factors identified in this study.

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“…To investigate this, we selected renal needle biopsies of two patients with medical histories of both chronic hypokalemia and nephropathy (estimated glomerular filtration rate Ͻ15) and compared them with appropriate controls. One case, previously described by Elitok et al (6), involved a patient who developed cachexia over the course of 2 yr because of an eating disorder. She ingested laxatives (bisacodyl) and nonsteroidal anti-inflammatory drugs (NSAIDs) regularly.…”

Section: Introductionmentioning

confidence: 99%

Patients with hypokalemia develop WNK bodies in the distal convoluted tubule of the kidney

Thomson

Schneider

Mutig

et al. 2019

American Journal of Physiology-Renal Physiology

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Hypokalemia contributes to the progression of chronic kidney disease, although a definitive pathophysiological theory to explain this remains to be established. K+ deficiency results in profound alterations in renal epithelial transport. These include an increase in salt reabsorption via the Na+-Cl− cotransporter (NCC) of the distal convoluted tubule (DCT), which minimizes electroneutral K+ loss in downstream nephron segments. In experimental conditions of dietary K+ depletion, punctate structures in the DCT containing crucial NCC-regulating kinases have been discovered in the murine DCT and termed “WNK bodies,” referring to their component, with no K (lysine) kinases (WNKs). We hypothesized that in humans, WNK bodies occur in hypokalemia as well. Renal needle biopsies of patients with chronic hypokalemic nephropathy and appropriate controls were examined by histological stains and immunofluorescence. Segment- and organelle-specific marker proteins were used to characterize the intrarenal and subcellular distribution of established WNK body constituents, namely, WNKs and Ste20-related proline-alanine-rich kinase (SPAK). In both patients with hypokalemia, WNKs and SPAK concentrated in non-membrane-bound cytoplasmic regions in the DCT, consistent with prior descriptions of WNK bodies. The putative WNK bodies were located in the perinuclear region close to, but not within, the endoplasmic reticulum. They were closely adjacent to microtubules but not clustered in aggresomes. Notably, we provide the first report of WNK bodies, which are functionally challenging structures associated with K+ deficiency, in human patients.

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Kaliopenic nephropathy revisited

Cited by 8 publications

References 15 publications

Late-onset Bartter syndrome type II

Late-onset Bartter syndrome type II

Pathophysiological Mechanisms by which Heat Stress Potentially Induces Kidney Inflammation and Chronic Kidney Disease in Sugarcane Workers

Patients with hypokalemia develop WNK bodies in the distal convoluted tubule of the kidney

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