Chronic kidney disease epidemic: How do we deal with it?

Chronic kidney disease (CKD) is a leading cause of mortality and morbidity around the world. The prevalence of CKD increases steadily over the past decade in parallel to the rapid expansion of diabetic population. Apart from increased mortality, CKD also has significant impact on quality of life and the economy. The approach to deal with the global CKD epidemic is multifaceted. Early detection by screening high-risk individuals such as those with hypertension and diabetes is important and cost-effective. However, low CKD awareness in many countries may impose barriers to early intervention. Hence raising CKD awareness among public and policy makers should be encouraged. In addition, the use of peritoneal dialysis, a less costly and home-based dialysis modality compared with in-center haemodialysis, should be promoted to maximize access to dialysis with limited resources. Finally, ongoing research and clinical trials through international collaborations could provide further insight into the pathophysiology of CKD progression, and establish the foundation for development of specific therapeutic agents to retard progression to end stage renal failure.

Expression of ACE and ACE2 in patients with hypertensive nephrosclerosis.

BACKGROUND: The interplay between intrarenal angiotensin-converting enzyme (ACE) and type 2 ACE (ACE2) might play important roles in the pathogenesis of hypertensive nephrosclerosis (HTN), but human data are limited. METHODS: Renal biopsy specimens of 41 patients with HTN and 10 transplant donors as controls (CTL) were studied. The glomerular and tubulointerstitial mRNA expression of ACE and ACE2 was measured by laser microdissection and real-time quantitative polymerase chain reaction. The corresponding protein level was determined by immunohistochemistry. RESULTS: Neither the glomerular nor tubulointerstitial mRNA expression of ACE or ACE2 correlated with the corresponding protein level by immunohistochemistry. The tubulointerstitial levels of ACE and ACE2 were significantly lower in HTN than CTL, while the glomerular ACE and ACE2 levels were similar between the groups. The tubulointersitial ACE and ACE2 levels significantly correlated with the estimated glomerular filtration rate (GFR) and inversely with the degree of histological damage. The glomerular ACE and ACE2 levels significantly correlated with the rate of GFR decline. The ratio of glomerular ACE and ACE2 level correlated with the estimated GFR and the degree of glomerulosclerosis. CONCLUSION: Our results suggest that intrarenal ACE and ACE2 may play an important role in the pathogenesis and progression of HTN. Studies based on the mRNA expression of ACE and ACE2 should be cautiously interpreted.

Intrarenal expression of microRNAs in patients with IgA nephropathy.

MicroRNAs (miRNAs) are noncoding, single-stranded RNA molecules that have important roles in a number of physiological and pathological processes. Previous studies have proved that miRNAs targeting ZEB1 and ZEB2 may repress epithelial-to-mesenchymal transition. In this work, we studied the intrarenal expression of miR-200 family, miR-205 and miR-192 in patients with immunoglobulin A (IgA) nephropathy. We studied 43 patients with biopsy-proven IgA nephropathy (IgA group). The intrarenal expression of miRNAs was quantified and compared with that of 15 patients with noninflammatory glomerulosclerosis (GS group) and 20 patients with nephrectomy for kidney cancer as controls (CTL group). The level of intrarenal miR-200c was downregulated, whereas the levels of intrarenal miR-141, miR-205 and miR-192 were upregulated in IgA but not GS group. Proteinuria significantly correlated with the intrarenal expression of miR-200c (r=-0.324, P=0.011) and glomerular filtration rate (GFR) significantly correlated with the intrarenal expression of miR-205 (r=-0.280, P=0.030). The degree of tubulointerstitial scarring correlated with miR-205 expression (r=0.389, P=0.021), whereas glomerulosclerosis correlated with miR-192 expression (r=-0.311, P=0.045). The rate of GFR decline significantly correlated with the intrarenal expression of miR-192 (r=0.373, P=0.015). The intrarenal expression of E-cadherin significantly correlated with the intrarenal expression of miR-200c (r=0.392, P=0.002). The results show that intrarenal expression of miR-200c, miR-141, miR-205 and miR-192 was diversely regulated and correlated with disease severity and progression in patients with IgA nephropathy. These miRNA species may be important in the pathogenesis and progression of IgA nephropathy.

The Oxford classification of IgA nephropathy: pathology definitions, correlations, and reproducibility.

Pathological classifications in current use for the assessment of glomerular disease have been typically opinion-based and built on the expert assumptions of renal pathologists about lesions historically thought to be relevant to prognosis. Here we develop a unique approach for the pathological classification of a glomerular disease, IgA nephropathy, in which renal pathologists first undertook extensive iterative work to define pathologic variables with acceptable inter-observer reproducibility. Where groups of such features closely correlated, variables were further selected on the basis of least susceptibility to sampling error and ease of scoring in routine practice. This process identified six pathologic variables that could then be used to interrogate prognostic significance independent of the clinical data in IgA nephropathy (described in the accompanying article). These variables were (1) mesangial cellularity score; percentage of glomeruli showing (2) segmental sclerosis, (3) endocapillary hypercellularity, or (4) cellular/fibrocellular crescents; (5) percentage of interstitial fibrosis/tubular atrophy; and finally (6) arteriosclerosis score. Results for interobserver reproducibility of individual pathological features are likely applicable to other glomerulonephritides, but it is not known if the correlations between variables depend on the specific type of glomerular pathobiology. Variables identified in this study withstood rigorous pathology review and statistical testing and we recommend that they become a necessary part of pathology reports for IgA nephropathy. Our methodology, translating a strong evidence-based dataset into a working format, is a model for developing classifications of other types of renal disease.

The Oxford classification of IgA nephropathy: rationale, clinicopathological correlations, and classification.

IgA nephropathy is the most common glomerular disease worldwide, yet there is no international consensus for its pathological or clinical classification. Here a new classification for IgA nephropathy is presented by an international consensus working group. The goal of this new system was to identify specific pathological features that more accurately predict risk of progression of renal disease in IgA nephropathy, thus enabling both clinicians and pathologists to improve individual patient prognostication. In a retrospective analysis, sequential clinical data were obtained on 265 adults and children with IgA nephropathy who were followed for a median of 5 years. Renal biopsies from all patients were scored by pathologists blinded to the clinical data for pathological variables identified as reproducible by an iterative process. Four of these variables: (1) the mesangial hypercellularity score, (2) segmental glomerulosclerosis, (3) endocapillary hypercellularity, and (4) tubular atrophy/interstitial fibrosis were subsequently shown to have independent value in predicting renal outcome. These specific pathological features withstood rigorous statistical analysis even after taking into account all clinical indicators available at the time of biopsy as well as during follow-up. The features have prognostic significance and we recommended they be taken into account for predicting outcome independent of the clinical features both at the time of presentation and during follow-up. The value of crescents was not addressed due to their low prevalence in the enrolled cohort.

Report of the Asian Forum of Chronic Kidney Disease Initiative (AFCKDI) 2007. "Current status and perspective of CKD in Asia": diversity and specificity among Asian countries.

The Japanese Society of Nephrology (JSN) sponsored the Asian Forum of CKD Initiative (AFCKDI) 2007 with the support of the International Society of Nephrology-Commission for Global Advancement in Nephrology (ISN-COMGAN), Asian Pacific Society of Nephrology (APSN), the Kidney Disease: Improving Global Outcome (KDIGO) and other national societies of nephrology in the Asian Pacific region on 27-28 May 2007 in Hamamatsu City, Japan. An international organising committee was established by leading experts of the CKD initiative. The main objective of this forum was to clarify the current status and perspectives of CKD and to promote coordination, collaboration and integration of initiatives in the Asian Pacific region. The forum received 56 papers from 16 countries; it began with the symposium "A Challenge to CKD in the world" and was followed by the ISN-COMGAN affiliated workshop "Current status and perspective of CKD in Asia". The second day was dedicated to discussion on the evaluation, surveillance and intervention in CKD in this area. At the end of the forum, we decided on the future plan as follows: (1) The AFCKDI will provide opportunities annually or biannually for every person who promotes CKD initiatives in the Asian Pacific region to join together and build consensus for action; (2) the second forum will be held in Kuala Lumpur on 4 May 2008 at the time of the 11th Asian Pacific Congress of Nephrology (APCN). Zaki Morad, President of the 11th APCN, will host the second forum; (3) the International Organising Committee (IOC) of the 1st AFCKDI will continue its function by adding other experts, including the organisers of the APCN; (4) the AFCKDI is not an organisation by itself, nor does it belong to any society, but is organised by each host national society of nephrology. The IOC will assist the domestic committee for the success of the forum and will assure the continuation of the mission; (5) in order to organise the forum and promote CKD initiatives in the Asia Pacific region, the AFCKDI will look for support by both national and international societies. The AFCKDI will keep an intimate and mutual relation with the ISN, APSN and KDIGO.

Isolate diffuse thickening of glomerular capillary basement membrane: a renal lesion in prediabetes?

A total of 23 patients with proteinuria and isolated ultrastructural diffuse thickening of the glomerular capillary basement membrane were studied, focusing on the possibility of diabetes mellitus, morphometry of the capillary basement membrane, and the comparison with three other groups of patients. These included 14 patients with minimal change nephropathy (MCN), 45 patients with type II diabetes arbitrarily divided into 11 early and 34 late diabetic patients, defined, respectively, as less than 3 and over 5 years history, and 13 patients biopsied for transient mild proteinuria or hematuria, with no evidence of renal disease on follow-up were used as controls. The level of proteinuria and prevalence of hematuria were similar in patients with isolated thick basement membrane and with diabetes. Diabetic retinopathy was present in 10% of early diabetes, 69% of late diabetes, but not in isolated thick basement membrane. Kimmelstiel-Wilson nodules were seen in late diabetes, and not in other patients. Hyaline arteriosclerosis was more common in late diabetes than in early diabetes or isolated thick basement membrane. The basement membrane thickness was similar between controls (371+/-17 nm) and MCN (345+/-16 nm), between patients with isolated thick basement membrane (482+/-69 nm) and early diabetes (457+/-64 nm), but significantly thicker in isolated thick basement membrane as compared to controls and MCN. In patients with isolated thick basement membrane, the basement membrane thickness was not correlated with age, smoking, body weight, hyaline arteriosclerosis, and hypertension. However, blood tests for diabetes were positive in 20% of patients at biopsy, in 44% at 6 months and 70% at 24 months follow-up, while seven patients showed no evidence of diabetes on follow-up. Patients with proteinuria and isolated thick glomerular basement membrane must be differentiated from MCN for therapeutic implications, and specifically managed for its strong association with prediabetes or early diabetes.