Chronic kidney disease (CKD), defined as the presence of irreversible structural or functional kidney damages, increases the risk of poor outcomes due to its association with multiple complications, including altered mineral metabolism, anemia, metabolic acidosis, and increased cardiovascular events. The mainstay of treatments for CKD lies in the prevention of the development and progression of CKD as well as its complications. Due to the heterogeneous origins and the uncertainty in the pathogenesis of CKD, efficacious therapies for CKD remain challenging. In this review, we focus on the following four themes: first, a summary of the known factors that contribute to CKD development and progression, with an emphasis on avoiding acute kidney injury (AKI); second, an etiology-based treatment strategy for retarding CKD, including the approaches for the common and under-recognized ones; and third, the recommended approaches for ameliorating CKD complications, and the final section discusses the novel agents for counteracting CKD progression.

Patients with chronic kidney disease-mineral and bone disorder (CKD-MBD) have a high risk of bone fracture because of low bone mineral density and poor bone quality. Osteoporosis also features low bone mass, disarranged microarchitecture, and skeletal fragility, and differentiating between osteoporosis and CKD-MBD in low bone mineral density is a challenge and usually achieved by bone biopsy. Bisphosphonates can be safe and beneficial for patients with a glomerular filtration rate of 30 mL/min or higher, but prescribing bisphosphonates in advanced CKD requires caution because of the increased possibility of low bone turnover disorders such as osteomalacia, mixed uremic osteodystrophy, and adynamic bone, even aggravating hyperparathyroidism. Therefore, bone biopsy in advanced CKD is an important consideration before prescribing bisphosphonates. Treatment also may induce hypocalcemia in CKD patients with secondary hyperparathyroidism, but vitamin D supplementation may ameliorate this effect. Bisphosphonate treatment can improve both bone mineral density and vascular calcification, but the latter becomes more unlikely in patients with stage 3-4 CKD with vascular calcification but no decreased bone mineral density. Using bisphosphonates requires considerable caution in advanced CKD, and the lack of adequate clinical investigation necessitates more studies regarding its effects on these patients.

The diagnosis of AA in HD patients was earlier than in non-HD patients. HD patients with AA had atypical presentations and a poor prognosis especially those that presented with hyponatremia and a perforated appendicitis. Higher C-reactive protein was associated with the development of perforated appendicitis in HD patients.

We describe a 17-year-old Chinese boy who presented with progressive muscle weakness and renal failure. He was diagnosed as BS of unknown type at the age of 9 months and treated with indomethacin (2 mg/kg/day) and potassium chloride (KCl) supplementation (1.5 mEq/kg/day) for hypokalemia (2.5 mmol/l). At the age of 12 years, serum K+ was 3.0 mmol/l and creatinine reached 2.0 mg/dl. On admission, his blood pressure was normal but volume status was depleted. Urinalysis was essentially normal. Biochemical studies showed hypokalemia (K+ 2.4 mmol/l) with a high transtubular K+ gradient (TTKG) 9.6, metabolic alkalosis (HCO3- 28.4 mmol/l), normomagnesemia (2.0 mg/dl), severe renal failure (BUN 94 mg/dl, Cr 6.3 mg/dl), and hypocalciuria (urine calcium/creatinine ratio 0.02 mg/mg). Abdominal sonography revealed bilateral small size kidneys without nephrocalcinosis or renal stones. After the withdrawal of indomethacin with regular KCl and adequate fluid supplementation for 1 year, serum creatinine and K+ levels have been maintained at 4.0 mg/dl and 3.3 mmol/l, respectively. Direct sequencing of NKCC2, ROMK, ClC-Kb, and NCCT in this patient disclosed a novel homozygous missense mutation (GGG to GAG, G470E) in CLCNKB. This G470E mutation was not identified in 100 healthy Chinese subjects. Long-term therapy of non-steroidal anti-inflammatory drugs (NSAIDs), prolonged hypokalemia, chronic volume depletion, and underlying genetic variety may contribute to the deterioration of his renal function. The cautious use of NSAIDs, aggressive correction of hypokalemia, and avoidance of severe volume depletion may prevent the irreversible renal damage in patients with BS due to a Cl- channel defect.

♦ Background: An approach to hyponatremia in uremic patients on peritoneal dialysis (PD) necessitates the assessment of intracellular fluid volume (ICV) and extracellular volume (ECV). The aim of the study was to evaluate the association of plasma sodium (Na + ) concentration and body fluid composition and identify the causes of hyponatremia in non-diabetic PD patients. ♦ Methods: Sixty non-diabetic uremic patients on PD were enrolled. Baseline body fluid composition, biochemistry, hand-grip test, peritoneal membrane characteristics, dialysis adequacy, Na + and water balance, and residual renal function (RRF) were measured. These parameters were reevaluated for those who developed hyponatremia, defined as serum Na + concentration < 132 mmol/L and a decline in serum Na + > 7 mmol/L, during monthly visits for 1 year. Body fluid composition was determined by multi-frequency bioelectrical impedance (BIA). ♦ Results: There was no significant correlation between serum Na + concentrations and any other parameters except a negative correction with overnight ultrafiltration (UF) amount (p = 0.02). The ICV/ECV ratio was positively correlated with serum albumin (p < 0.005) and hand grip strength (p < 0.05). Over 1 year, 9 patients (M:F = 3:6, aged 35 -77) with 4 different etiologies of hyponatremia were identified. Hyponatremic patients with a body weight (BW) loss had either an increased ICV/ECV ratio associated with primarily a negative Na + balance (n = 2) or a reduced ratio of ICV/ECV associated with malnutrition (n = 2). In contrast, hyponatremic patients with a BW gain had either a reduced ICV/ECV ratio associated with a rapid loss of RRF and a higher peritoneal permeability (n = 2) or a normal to increased ICV/ECV ratio associated with high water intake (n = 3). ♦ Conclusion: Besides BW change and ultrafiltration rate, the assessment of ICV/ECV ratio is valuable in identifying the etiologies of hyponatremia in PD and provides a guide for optimal therapy.

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Recurrent mutations in the SLC12A3 gene responsible for autosomal recessive Gitelman syndrome (GS) are frequently reported, but the exact prevalence is unknown. The rapid detection of recurrent SLC12A3 mutations may help in the early diagnosis of GS. This study was aimed to investigate the prevalence of recurrent SLC12A3 mutations in a Taiwan cohort of GS families and develop a simple and rapid method to detect recurrent SLC12A3 mutations. One hundred and thirty independent Taiwan families with genetically confirmed GS were consecutively enrolled to define recurrent SLC12A3 mutations and determine their prevalence. Using TaqMan probe-based real-time polymerase chain reaction, we designed a mutation detection plate with all recurrent mutations. We validated this mutation detection plate and tested its feasibility in newly diagnosed GS patients. A total of 57 mutations in the SLC12A3 gene were identified and 22 including 2 deep intronic mutations were recurrent mutations consisting of 87.1% (242/278, 18 triple) of all allelic mutations. The recurrent mutation-based TaqMan assays were fully validated with excellent sensitivity and specificity in genetically diagnosed GS patients and healthy subjects. In clinical validation, recurrent mutations were recognized in 92.0% of allelic mutations from 12 GS patients within 4 h and all were confirmed by direct sequencing. Recurrent SLC12A3 mutations are very common in Taiwan GS patients and can be rapidly identified by this recurrent mutation-based SLC12A3 mutation plate.