Clinical Journal of the American Society of Nephrology Mini-Reviews

The Alphabet Soup of Kidney Transplantation: SCD, DCD, ECD--Fundamentals for the Practicing Nephrologist

Rao, P. S., Ojo, A. — Tue, 03 Nov 2009 10:02:23 PST

There is significant variability in the quality of deceased-donor kidneys that are used for transplantation. The quality of the donor kidney has a direct effect on important clinical outcomes such as acute rejection, delayed graft function, and patient and allograft survival. Expanded-criteria donors (ECDs) refer to older kidney donors (≥60 yr) or donors who are aged 50 to 59 yr and have two of the following three features: Hypertension, terminal serum creatinine >1.5 mg/dl, or death from cerebrovascular accident. By definition, ECD kidneys have a 70% greater likelihood of failure compared with one from a 35-yr-old male donor who died from a motor vehicle accident. Donation after cardiac death (DCD) is a small but rapidly growing fraction of donors. An ECD kidney transplant recipient has a projected average added-life-years of 5.1 yr compared with 10 yr for a kidney recipient from a standard-criteria donor. Kidney transplantation from DCD seems to have similar allograft and patient survival compared with kidney from donation after brain death; however DCD transplantation has a 42 to 51% risk for delayed graft function (need for at least one dialysis treatment during the first week after transplantation) compared with 24% in an standard-criteria donor kidney transplant. Familiarity with the comprehensive allocation rules governing different categories of deceased-donor kidneys by the nephrologists and dialysis team providers is essential to maximizing patient autonomy and to improve the outcomes of kidney transplantation.

Measurement and Estimation of GFR in Children and Adolescents

Schwartz, G. J., Work, D. F. — Tue, 03 Nov 2009 10:02:23 PST

GFR is the best indicator of renal function in children and adolescents and is critical for diagnosing acute and chronic kidney impairment, intervening early to prevent end-stage renal failure, prescribing nephrotoxic drugs and drugs cleared by a failing kidney, and monitoring for side effects of medications. Renal inulin clearance was the gold standard for GFR but is compromised by lack of availability, difficult assays, and problems of collecting timed urine samples, especially in children with vesicoureteral reflux or bladder dysfunction. Creatinine clearance-based estimates of GFR are often used in pediatrics. The addition of cimetidine to eliminate creatinine secretion permits accurate measurement of GFR in those who can completely empty their bladders to provide timed urine collections. Radioisotopes are used in plasma disappearance GFR determinations; however, these are not ideal for use in children, especially for repeated studies. The plasma disappearance of iohexol serves as a promising alternative GFR marker, because it is safe and not radioactive, easily measured, not metabolized or transported by the kidney, and excreted primarily by glomerular filtration. GFR estimating equations, based on serum concentrations of creatinine or cystatin C, are popular clinically and in research studies. Efforts are ongoing to improve these estimating equations for children and make the results readily available to clinicians obtaining standard chemistry profiles, as is being done for adults. However, at this time, there is no dependable substitute for an accurately determined GFR, and iohexol plasma disappearance offers the best combination of safety, accuracy, and reproducible precision.

Interstitial Cystitis: An Unsolved Enigma

Moutzouris, D.-A., Falagas, M. E. — Tue, 03 Nov 2009 10:02:23 PST

Painful bladder syndrome/interstitial cystitis (PBS/IC) is a chronic disease of unknown etiology characterized by vague bladder pain and nonspecific urinary symptoms, such as urgency and frequency. Although it was initially considered to be a rare condition, its prevalence has significantly increased, possibly because of different definitions used and greater physician awareness. Because of the multiple diagnostic criteria used, there is significant variation in its prevalence. In addition, there is often a delay in the diagnosis of PBS/IC. It affects predominantly women of middle age, and it significantly decreases quality of life. Diagnosis of PBS/IC is mainly a diagnosis of exclusion; there are no characteristic symptoms or pathognomonic findings. Therefore, it is important to rule out diseases that have a similar clinical picture (i.e., urinary infections, bladder carcinoma) but definite therapies and worse prognosis if left untreated. PBS/IC management suffers from lack of evidence; many therapies are empiric or based on small studies and case series. Treatment includes supportive therapies (psychosocial, behavioral, physical), oral treatments, and intravesical treatments, whereas other more invasive treatments such as electric neuromodulation and reconstructive surgery are reserved for refractory cases. Physicians should always keep in mind the diagnosis of PBS/IC in patients presenting with chronic urinary symptoms after excluding other more common diseases.

Biomarkers for Lupus Nephritis: The Quest Continues

Rovin, B. H., Zhang, X. — Tue, 03 Nov 2009 10:02:23 PST

Current treatment of severe lupus nephritis is unsatisfactory in terms of both outcome and toxicity. To improve the efficacy and decrease the adverse effects of immunosuppression, it would be ideal to be able to predict the course and pathology of lupus nephritis and adjust therapy appropriately. This will require biomarkers that reflect disease activity. Recently, significant effort has been put into identifying biomarkers that can anticipate impending lupus renal flare, forecast development of chronic kidney disease, or reflect kidney histology at the time of flare. Although these biomarkers are potentially useful, to date none has been clinically validated in a large, prospective cohort of patients with SLE. This article reviews the current status of lupus nephritis biomarker investigation and articulates a perspective of how future efforts should be focused.

Immunosuppressive Drugs and Tregs: A Critical Evaluation!

De Serres, S. A., Sayegh, M. H., Najafian, N. — Mon, 05 Oct 2009 10:02:28 PDT

To define therapeutic strategies that promote tolerance, it is of critical importance to determine the effects of immunosuppressive drugs on regulatory T cells (Tregs). This review discusses the current knowledge about the physiology of Tregs in humans, the role or Tregs in transplantation, and the impact of the different types of immunosuppressive agents on the frequency and functionality of Tregs in in vitro and in vivo systems.

Can We Personalize Treatment for Kidney Diseases?

Rovin, B. H., McKinley, A. M., Birmingham, D. J. — Mon, 05 Oct 2009 10:02:28 PDT

The idea of individualizing therapies to obtain optimal clinical results is not new but has only recently been applied to kidney diseases. Nonetheless, kidney disorders present a variety of opportunities to personalize medicine. Here, the heterogeneity of kidney disorders is reviewed to provide a rationale for pursuing personalized medicine. Data on adjusting therapy on the basis of pharmacogenetics/genomics and pharmacodynamics are summarized to demonstrate where the field is, and biomarker studies that reflect the future of personalized medicine are discussed. The goal of this review is to demonstrate that we can personalize therapy for kidney diseases but that considerable investment in new research will be required for personalized medicine to be routinely used in nephrology clinics.