Vascular age is associated with the risk of dialysis or death in chronic kidney disease.

AIM: Increased arterial stiffness is associated with progressive renal deterioration and poor clinical outcomes in patients with chronic kidney disease (CKD). Assessment of vascular age as derived from arterial stiffness parameters might be an important clinical marker of cardiovascular risks. The aim of the present study is to evaluate whether the difference (△age) between vascular age and chronological age can predict the risk of reaching dialysis or death in patients with known CKD. METHODS: This longitudinal study enrolled 94 male Chinese CKD patients, aged 40-62 years. Vascular age was calculated by brachial-ankle pulse wave velocity, and measured by an ankle-brachial index-form device. The study endpoints were the commencement of renal replacement therapy or death. RESULTS: After a stepwise multivariate analysis, △age was associated independently with increased urine protein-to-creatinine ratio (ß = 0.32; P = 0.001) and decreased baseline estimated glomerular filtration rate (ß = -0.24; P = 0.008). During a median follow-up period of 62 (interquartile range = 55-66) months, the 4-year cumulative incidence of reaching the study endpoint in patients with △age = 0 and △age > 0 year was 4.9% and 25%, respectively (log-rank test, P = 0.009). Multivariate forward Cox regression analysis identified that higher △age (hazard ratio (HR) = 1.05; P = 0.027), lower baseline estimated glomerular filtration rate (HR = 0.93; P < 0.001), and history of cardiovascular disease (HR = 5.90; P = 0.031) were independently associated with progression to commencement of dialysis or death. CONCLUSION: Thus, the assessment of the difference between vascular age and chronological age may provide an alternative method to identify CKD patients at a high risk of progression to dialysis or death.

CKD prevention: Perspectives in Hong Kong.

Hong Kong experiences a progressive rise in the prevalence of treated end-stage renal disease (ESRD) as recorded by the Hong Kong Renal Registry managed by the Hospital Authority (HA) that takes care of 90 - 95% of the ESRD burden. The CKD burden is envisaged to be high, as reflected by 2 initiatives - SHARE which detected a high prevalence of urine or blood pressure abnormalities among 1,201 asymptomatic individuals who underwent screening, and RISKS that aimed to further characterize the spread of CKD in the asymptomatic population. For CKD prevention, two statutory bodies - the HA and Hong Kong College of Physicians (HKCP), and two non-governmental organizations - Hong Kong Society of Nephrology (HKSN) and Hong Kong Kidney Foundation (HKKF), all have a role to play. The Central Renal Committee (CRC) operated under HA co-produces with HKCP and HKSN a clinical practice guideline for the provision of renal service in Hong Kong which includes CKD care and prevention. HKSN now holds annual educational symposia and a Continuous Medical Education (CME) course in partnership with the HKCP and Asian Pacific Society of Nephrology in addition to its Annual Scientific Meeting. The HKSN also provides a collective International Society of Nephrology (ISN) membership for all its full members to enhance education and other pertinent initiatives. For public education, the HKSN and HKKF participate in the annual World Kidney Day event and organize free blood pressure and CKD surveys in public housing estates to increase public awareness of CKD. The latter is also effected via regular promotion through the mass media.

Non-invasive assessment of kidney allograft fibrosis with shear wave elastography: A radiological-pathological correlation analysis.

OBJECTIVES: To evaluate the use of shear wave elastography in assessment of kidney allograft tubulointerstitial fibrosis. METHODS: Shear wave elastography assessment was carried out by two independent operators in kidney transplant recipients who underwent allograft biopsy for clinical indications (i.e. rising creatinine >15% or proteinuria >1 g/day). Allograft biopsies were interpreted by the same pathologist according to the 2013 Banff Classification. RESULTS: A total of 40 elastography scans were carried out (median creatinine 172.5 µmol/L [interquartile range 133.8-281.8 µmol/L]). Median tissue stiffness at the cortex (22.6 kPa [interquartile range 18.8-25.7 kPa] vs 22.3 kPa [interquartile range 19.0-26.5 kPa], P = 0.70) and medulla (15.0 kPa [interquartile range 13.7-18.0 kPa] vs 15.6 kPa [interquartile range 14.4-18.2 kPa]) showed no significant differences between the two observers. Interobserver agreement was satisfactory (intraclass correlation coefficient of the cortex 0.84, 95% CI 0.70-0.92 and intraclass correlation coefficient of the medulla 0.88, 95% CI 0.78-0.94). The areas under the receiver operating characteristic curves for detection of tubulointerstitial fibrosis were estimated to be 0.75 (95% CI 0.61-0.89), 0.85 (95% CI 0.75-0.95) and 0.65 (95% CI 0.53-0.78) for cortical, medullary tissue stiffness and serum creatinine, respectively. CONCLUSIONS: Shear wave elastography can be used as a non-invasive tool to evaluate kidney allograft fibrosis with reasonable interobserver agreement and superior test performance to serum creatinine in detecting early tubulointerstitial fibrosis.

The kallikrein-kinin system.

Emerging evidence suggests a role of the kallikrein-kinin system (KKS) in the pathogenesis of diabetic nephropathy (DN). Tissue kallikrein 1 is a member of the tissue kallikrein family that is mainly responsible for the generation of kinins, and bradykinin (BK) is the principal kinin responsible for the biologic actions of the KKS that acts through the ubiquitous BK 2receptor (B2R) and the inducible B1R. In the kidney, all KKS components are expressed. In particular, kallikrein 1 that is traditionally thought to be solely confined to the distal nephron has recently been identified in the proximal tubule of the human diabetic kidney. Current evidence suggests conflicting roles of the KKS in DN. For a renoprotective role of the KKS, BK reduces mesangial cell proliferation under the diabetic milieu; Akita B2R-/- or STZ-induced KLK-/- mice (T1DM) have more severe albuminuria and glomerulosclerosis, while antagonizing the B2R with icatibant attenuates the antiproteinuric effect of ramiprilin db/db mice (T2DM). For a detrimental role of the KKS, BK upregulates tubular cell IL-6, CCL-2, and TGF-ß expression via ERK1/2 activation; the B2R-/- status protects against the development of DN lesions in STZ-injected mice, while blocking B2R with icatibant alleviates biochemical and histologic injuries in uninephrectomized db/db mice. These opposite findings may arise from multiple factors and call for further evaluation to clarify the role of the KKS in DN and diabetic tubulopathy.

Prospective controlled study on mycophenolate mofetil and prednisolone in the treatment of membranous nephropathy with nephrotic syndrome.

BACKGROUND: Retrospective and anecdotal data suggest that mycophenolate mofetil (MMF) might be effective when given as rescue therapy for membranous nephropathy (MN). Prospective controlled data on MMF and prednisolone as primary therapy are lacking. METHODS: A prospective, randomized, controlled, open-label study was performed to investigate the efficacy and tolerability of MMF and prednisolone as primary treatment in MN with nephrotic syndrome. MMF and prednisolone given for 6 months was compared against a modified Ponticelli regimen in 20 patients, with follow up of 15 months. RESULTS: MMF with prednisolone and the comparative immunosuppressive regimen showed similar efficacy in proteinuria reduction, despite a lower cumulative prednisolone dose in the MMF group (3.80 +/- 0.28 vs 9.93 +/- 0.25 g, P < 0.001). Remission (composite of 'complete' and 'partial') rates were 63.6% and 66.7% in the MMF group and control group, respectively (P = 1.000). Serum creatinine and creatinine clearance remained stable during follow up. Cumulative relapse rate was 23.1% at 2 years. Chlorambucil resulted in more leucopenia compared with MMF. CONCLUSION: Data from this pilot study indicate that more than 60% of patients with MN and nephrotic syndrome respond to combined MMF and prednisolone treatment, and suggest potential benefits of MMF as being steroid-sparing and having less adverse effects compared with other commonly used cytotoxic agents.

Differential expression of aquaporins in the kidneys of streptozotocin-induced diabetic mice.

BACKGROUND AND AIM: Aquaporins (AQPs) are members of the water channel family and are important in renal physiology as it affects urinary concentration. The downregulation of aquaporins is often observed in polyuria associated with acquired nephrogenic diabetes insipidus. In this study, we examined the expression of AQP1, AQP2, AQP3 and AQP4 in streptozotocin (STZ)-induced diabetic mice. RESULTS: By semiquantitative reverse transcription-polymerase chain reaction, we detected no change in the gene expression of AQP1 or AQP4 in whole kidney among STZ-induced diabetic mice (STZ mice) and sham (control group that received citrate buffer injection only). In contrast, we found less AQP2 or AQP3 mRNA expression in the whole kidney from STZ mice. Immunoblotting studies confirmed no difference in AQP1 or AQP4 protein expression of whole kidney between STZ mice and sham. However, there was less AQP2 or AQP3 protein expression in the whole kidney from STZ mice as compared to sham. By immunochemical staining, the reduction of AQP2 protein was localized to the principle cells of the collecting ducts. The expression of cortical AQP3 (especially the outer cortex, the S1 and S2 segments of the proximal tubules) was downregulated in STZ mice whereas the expression of AQP3 protein in medullary collecting ducts was similar to that of sham. CONCLUSION: Our results reveal that the water transport in urinary concentration involves the downregulation of AQP2 and AQP3 expression in STZ mice.