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Pseudohypoaldosteronism type II (PHAII) is a hereditary disease characterized by salt-sensitive hypertension, hyperkalemia and thiazide sensitivity. Mutations in with-no-lysine kinase 1 (WNK1) and WNK4 genes are reported to cause PHAII. Rigorous studies have demonstrated that WNK kinases constitute a signaling cascade with oxidative stress-responsive gene 1 (OSR1), Ste20-related proline-alanine-rich kinase (SPAK) and the solute carrier family 12a (SLC12a) transporter, including thiazide-sensitive NaCl cotransporter. The WNK-OSR1/ SPAK-SLC12a signaling cascade is present in the kidneys and vascular smooth muscle cells (VSMCs) and regulates salt sensitivity physiologically, i.e. urinary sodium excretion and arterial tone by various hormonal and dietary factors. However, although it was clear that the abnormal activation of this signaling cascade is the molecular basis of PHAII, the molecular mechanisms responsible for the physiological regulation of WNK signaling and the effect of WNK4 mutations on PHAII pathogenesis are poorly understood. Two additional genes responsible for PHAII, Kelch-like 3 (KLHL3) and Cullin 3 (CUL3), were identified in 2012. WNK1 and WNK4 have been shown to be substrates of KLHL3-CUL3 E3 ubiquitin ligase both in vitro and in vivo. In PHAII, the loss of interaction between KLHL3 and WNK4 induces increased levels of WNK kinases due to impaired ubiquitination. These results indicate that WNK signaling is physiologically regulated by KLHL3/CUL3- mediated ubiquitination. Here, we review recent studies investigating the pathophysiological roles of the WNK signaling cascade in the kidneys and VSMCs and recently discovered mechanisms underlying the regulation of WNK signaling by KLHL3 and CUL3. [ABSTRACT FROM AUTHOR]

The article presents a case of a 78-year-old Japanese woman with a rapid course of nephrotic syndrome. In the study, a renal biopsy is conducted which showed lobular glomerulopathy and membranoproliferative glomerulonephritis-like lesions on light microscopy. This case was diagnosed as fibronectin glomerulopathy.

The article presents a case study of a 20-year-old man suffering from edema. The patient was diagnosed of having acute poststreptococcal glomerulonephritis (APSGN) with acute interstitial nephritis (AIN). An overview of his administration with methylprednisolone pulse therapy and analysis on the association of the disease to streptococcal pyrogenic exotoxin B is also provided.