Christopher G. Winearls

An epidemic of chronic kidney disease: fact or fiction?

The publication of the Kidney Disease Outcomes and Quality Initiative (KDOQI) clinical practice guidelines for the evaluation, classification and stratification of chronic kidney disease (CKD) in February of 2002 was a landmark event [1]. This effort has profoundly impacted clinical practice, helped bring some order to a chaotic system of nomenclature and stimulated a resurgence of interest in this longneglected domain of clinical nephrology [2]. The nephrology community is now using a definition of the five stages of CKD, based on the presence of ‘kidney damage’ and/or reduced estimated glomerular filtration rate (eGFR) for 3 months or more [1,3]. However, it is noteworthy that three of the five stages of CKD (stages 3, 4 and 5) were arbitrarily defined and based solely on the absolute threshold of eGFR (standardized to 1.73 m2 body surface area) without any requirement for concomitant evidence of ‘kidney damage’, such as proteinuria or adjustment for age and gender [2]. These levels of eGFR, combined with the similarly arbitrary selection of a time dimension (≥3 months) for their persistence to establish ‘chronicity’, became the ‘gold-standard’ for definition of a ‘disease’. The abbreviated modification of diet in renal disease (MDRD) equation for deriving an estimate of true glomerular filtration rate (GFR) from values of serum creatinine (calibrated to the standard used to derive the formula) quickly became the most widely used method for determination of eGFR, despite its lack of validation in subjects without CKD or across a wide spectrum of ages, body habitus, diet, ethnicity and geographic location [4]. Because of inaccuracies, relative to true GFR, when eGFR is >60 ml/min/1.73 m2 reporting of specific values of eGFR was recommended only when calculated values of <60 ml/min/1.73 m2 were obtained [5]. Despite

Screening for CKD with eGFR: doubts and dangers.

The early identification of chronic kidney disease (CKD) is a legitimate enterprise if it provides meaningful opportunities for effective and safe interventions that reduce the risk of death, end-stage renal disease, or complications of renal dysfunction. The screening of unselected populations not already known to be at risk of CKD has the potential of harm and has not been shown to be cost-effective. The application of formulas for the estimation of GFR (eGFR) to the guidelines for staging of chronic kidney disease (Kidney Disease Outcomes Quality Initiative, K/DOQI) as universal screening tools is of dubious value and has inherent dangers. This conclusion is based both on the unreliability of current formulas for determining eGFR and flaws in the K/DOQI schema for staging of CKD. The failure to take into account the normal age- and gender- associated decline in GFR and the lack of a requirement for other evidence of kidney disease in CKD stage 3 leads to an erroneous categorization of large numbers of mostly elderly and female subjects as having an intermediate stage of a lethal disease. Criteria for CKD staging should take into account the percentile distribution of eGFR by age and gender. Targeted screening for CKD is likely to be more cost-effective than universal screening. Whether early identification and treatment of subjects with reduced levels of GFR within the normal range for their age/gender, but without any other manifestations of kidney disease, will reduce the subsequent risk of cardiovascular events or progression to end-stage-renal disease is currently unproven.

The Global Burden of Chronic Kidney Disease: How Valid Are the Estimates?

Background/Aims: The values for the global prevalence of chronic kidney disease (CKD) are poorly understood. Current classification schemas may overstate the prevalance of CKD. This minireview analyzes the pitfalls in the use of current classification approaches for identifying CKD on a global basis. Methods: Literature review and comment. Results: Published estimates for the global burden of CKD are likely to be incorrect and inflated. Overestimations of prevalence have occurred due to flaws in the classification systems employed and in ascertainment methods. Conclusions: A revision of the current system of diagnosing and classifying CKD is needed in order to determine with greater precision true global burden of CKD. A new system is proposed.

Classification of Chronic Kidney Disease in the Elderly: Pitfalls and Errors

The average glomerular filtration rate (GFR) is lower in the elderly than in the young and is usually a consequence of biological ageing, the rate of which varies between individuals. In some subjects, the decline is aggravated by concomitant vascular disease. The prevalence of significant kidney disease in the elderly has been overestimated – largely by rendering a diagnosis of chronic kidney disease by reference to estimates of GFR which are found in the young. A stable low GFR in the elderly, provided it is physiologically sufficient to meet homeostatic demands, is not a disease per se and seldom progresses to true kidney failure. However, it can be a risk factor for acute kidney injury drug misdosing, and possibly cardiovascular disease, so it should be noted.

Diagnosing chronic kidney disease.

Purpose of reviewTo review the current state-of-the art in diagnosing chronic kidney disease (CKD) using classification systems based on estimated glomerular filtration rate (eGFR) and kidney damage. Recent findingsCKD, as defined by current classification systems, has many pitfalls, but the presence and stage of CKD has important value in determining prognosis, particularly when the effects of albuminuria are added to eGFR SummaryThe diagnosis of CKD using current classification schema based on eGFR alone needs to be approached with some caution, particularly in the elderly without concomitant signs of kidney damage. The presence and magnitude of albuminuria has important diagnostic and prognostic significance.

Objective monitoring of disease activity in polyarteritis by measurement of serum C reactive protein concentration.

Serial measurements of the serum concentration of C reactive protein were made in 27 patients with polyarteritis over six years. The concentration was invariably raised when the disease was active, even in patients receiving immunosuppressive treatment, and fell rapidly in association with clinical remission induced by immunosuppression. During periods of complete remission, in the absence of any intercurrent condition, the value remained within the normal range. The correlation between C reactive protein concentration and disease activity was much closer than that between erythrocyte sedimentation rate and disease activity. These results indicate that serial measurement of the serum C reactive protein concentration fills the urgent need for an objective index of the activity of polyarteritis and its response to treatment.

Novel approaches for reducing free light chains in patients with myeloma kidney

Myeloma kidney is a tubulointerstitial pathology that accounts for approximately 80–90% of severe acute kidney injury in patients with multiple myeloma. Unless there is rapid intervention, progressive irreversible damage from interstitial fibrosis and tubular atrophy occurs. Work over the past decade has demonstrated that an early sustained reduction in serum concentrations of pathogenic monoclonal free light chains (FLCs) leads to improved renal recovery rates. In turn, an early improvement in renal function is associated with improved patient survival. An early reduction in FLC levels should therefore become standard of care, although the optimum mechanisms to achieve this depletion of FLCs remain to be determined. To provide a coordinated, cross-disciplinary approach to research in this disease, the International Kidney and Monoclonal Gammopathy Research Group was formed. In this Review, we address the current state of knowledge in the management of myeloma kidney.

Routine reporting of estimated glomerular filtration rate: not ready for prime time

According to the Kidney Disease Outcomes Quality Initiative guidelines, estimated glomerular filtration rate can be used to diagnose chronic kidney disease. The authors of this Viewpoint argue, however, that reliance on estimated glomerular filtration rates alone encourages an erroneous disregard of age, gender and other evidence of kidney disease, such as proteinuria. Consequently, mandatory reporting of estimated glomerular filtration rate leads to misdiagnosis of chronic kidney disease and to the unhelpful referral of healthy individuals to nephrologists.

Serum C-reactive protein concentration in the management of infection in patients treated by continuous ambulatory peritoneal dialysis.

In a prospective study over 21 months, serum C-reactive protein (CRP) concentration was measured serially in 39 consecutive patients undergoing continuous ambulatory peritoneal dialysis. All patients with peritonitis mounted a CRP response, and the height of the response correlated well with the severity and extent of the peritoneal damage. Patients who recovered uneventfully after antimicrobial treatment showed a prompt fall in CRP from its peak value towards normal. In contrast, each patient in whom the serum CRP value remained raised after antimicrobial treatment had a complicated course. During routine outpatient follow up the serum CRP value remained within the normal range in the absence of intercurrent complications. These results, together with the commercial availability of rapid and precise assays for CRP, indicate that serial CRP measurements may be useful in monitoring the efficacy of antimicrobial treatment during episodes of peritonitis and in the recognition of intercurrent complications in patients undergoing continuous ambulatory peritoneal dialysis.

A proposal for standardized grading of chronic changes in native kidney biopsy specimens

Chronic changes represent an important component of native kidney biopsy evaluation and have a major bearing on predicting prognosis and guiding treatment. We propose here a uniform, semiquantitative approach to assessing such changes, which include glomerulosclerosis, tubular atrophy, interstitial fibrosis, and arteriosclerosis, and we report these findings as an overall chronicity grade.