A series of problems including osteopathy, abnormal serum data, and vascular calcification associated with chronic kidney disease (CKD) are now collectively called CKD-mineral bone disease (CKD-MBD). The pathophysiology of CKD-MBD is becoming clear with the emerging of αKlotho, originally identified as a progeria-causing protein, and bone-derived phosphaturic fibroblast growth factor 23 (FGF23) as associated factors. Meanwhile, compared with calcium and parathyroid hormone, which have long been linked with CKD-MBD, phosphate is now attracting more attention because of its association with complications and outcomes. Incidentally, as the pivotal roles of FGF23 and αKlotho in phosphate metabolism have been unveiled, how phosphate metabolism and hyperphosphatemia are involved in CKD-MBD and how they can be clinically treated have become of great interest. Thus, the aim of this review is reconsider CKD-MBD from the viewpoint of phosphorus, its involvement in the pathophysiology, causing complications, therapeutic approach based on the clinical evidence, and clarifying the importance of phosphorus management.

Autosomal dominant polycystic kidney disease (ADPKD) patients with PKD1 mutations, particularly those with truncating mutations, show poor prognosis. However, the differences in disease progression with different mutation types are unclear. Here, a comparative study was conducted on the renal prognosis of patients with ADPKD who were categorized based on genotype (PKD1 versus PKD2 mutation), mutation type (truncating mutation: nonsense, frameshift, splicing mutation, and large deletion; non-truncating mutation: substitution and in-frame deletion), and mutation position. A total of 123 patients visiting our hospital were enrolled. Renal prognosis was poor for those with PKD1 splicing, PKD1 frameshift, and PKD2 splicing mutations. Despite the truncating mutation, the renal prognosis was relatively favorable for patients with nonsense mutations. Three out of five patients with PKD2 mutation required renal replacement therapy before 58 years of age. In conclusion, we showed that renal prognosis differs according to mutation types in both PKD1 and PKD2, and that it was favorable for those with nonsense mutations among patients with PKD1 truncating mutations. It was also confirmed that renal prognosis was not always favorable in patients with PKD2 mutations. A detailed assessment of mutation types may be useful for predicting the renal prognosis of patients with ADPKD.

The progression of immunoglobulin A nephropathy (IgAN) is currently assessed using the Oxford MEST-C score, which uses five indicators (mesangial and endocapillary hypercellularity, segmental sclerosis, interstitial fibrosis/tubular atrophy, and the presence of crescents) but has not yet included any risk factors related to glomerular size. Therefore, we tested whether adding another indicator, maximal glomerular diameter (Max GD), would improve the prognostic ability of this scoring system. The data of 101 adult patients diagnosed with IgAN between March 2002 and September 2004 were reviewed. We used McFadden’s pseudo-R² and the corrected Akaike information criterion to assess model fit and the concordance (C)-statistic to assess discriminatory ability. A 10 μm increase in Max GD was significantly associated with a composite outcome (≥50% decline in the estimated glomerular filtration rate or end-stage renal disease). The receiver operating characteristic analysis determined the cut-off for high vs. low Max GD at 245.9 μm, and adding high Max GD to the MEST-C score significantly improved the model’s discrimination of renal outcomes at 5 and ≥10 years. Thus, including the Max GD in the Oxford classification of IgAN might increase its robustness and provide a more comprehensive prognostic system for clinical settings.

Studies on sex differences in time-series changes in pseudo-R² values regarding hyperuricemia (HU) in relation to the kidney prognosis among patients with chronic kidney disease (CKD) are scant. The kidney prognosis was evaluated in 200 patients with CKD (median follow-up, 12.3 years). Survival analyses and logistic regression analyses were conducted, generating time-series pseudo-R² values. We used four definitions of HU according to serum uric acid (SUA) levels (HU6, SUA ≥ 6.0 mg/dL; HU7, SUA ≥ 7.0 mg/dL; HU8, SUA ≥ 8.0 mg/dL) and antihyperuricemic agent use to calculate the mean and percentage of the change in pseudo-R² values from the 6th year until the end of the study (6Y–End Mean and 6Y–End Change, respectively). The multivariable Cox regression analysis showed that HU7 was significantly associated with kidney outcomes. When stratified by sex, the 6Y–End Mean was clearly higher in women than in men for all HU definitions, with the highest value (0.1755) obtained for HU7 in women. The pseudo-R² values for HU6 in women showed an increasing pattern, with a 6Y–End Change of 11.4%/year. Thus, it may be clinically meaningful to consider sex differences in the time-series pseudo-R² values regarding HU and kidney outcomes.

Background: It is not well known whether diabetic peripheral neuropathy diagnosed using a non-invasive point-of-care nerve conduction device called DPN-Check^® is associated with diabetic nephropathy. Thus, we aimed to evaluate the association of diabetic peripheral neuropathy with urinary albumin excretion in patients with type 2 diabetes using DPN-Check^®. Methods: This retrospective observational study included 323 Japanese patients with type 2 diabetes. The urinary albumin-to-creatinine ratio in a spot urine sample was defined as urinary albumin excretion. Multiple linear regression analysis was used to determine the association of DPN-Check^®-determined diabetic peripheral neuropathy with urinary albumin excretion. Results: Patients with DPN-Check^®-determined diabetic peripheral neuropathy had significantly higher urinary albumin excretion than those without, while there was no difference in urinary albumin excretion between patients with and without diabetic peripheral neuropathy determined by simplified diagnostic criteria. In the multivariate model, the DPN-Check^® determined that diabetic peripheral neuropathy was significantly associated with urinary albumin excretion even after adjustment for covariates (standardized β, 0.123; p = 0.012). Conclusions: Our study found a significant association between diabetic peripheral neuropathy diagnosed using DPN-Check^® and urinary albumin excretion in patients with type 2 diabetes.

Background: Serum phosphate levels, which are associated with the progression of renal dysfunction in chronic kidney disease, in patients with autosomal dominant polycystic kidney disease (ADPKD) are lower than those in patients with other kidney diseases. However, their role in ADPKD remains unclear. This study aimed to determine whether serum phosphate levels could have an association with renal prognoses among patients with ADPKD. Methods: In total, 55 patients with PKD1 or PKD2 mutations but not undergoing dialysis were evaluated. Data regarding serum phosphate levels were collected, and Cox regression analyses were used to calculate hazard ratios (HRs) with renal replacement therapy as the endpoint. Results: The median (quartile 1; quartile 3) serum phosphate concentration was 3.4 (3.1; 3.9) mg/dL, and the estimated glomerular filtration rate (eGFR) was 39.5 (17.6; 65.7) mL/min/1.73 m². The multivariate analysis that included age, PKD1 mutation, eGFR, urinary protein excretion, hyperuricemia, and serum phosphate determined that eGFR (HR, 0.82; 95% confidence interval (CI), 0.74–0.90; p < 0.0001) and serum phosphate (HR, 6.78; 95% CI, 1.94–34.02; p = 0.0021) were independently associated with renal replacement therapy. Conclusions: We found that serum phosphate levels were significantly associated with poor renal prognoses in patients with ADPKD.