Blog entry by Denise Smith
'Ideal Criteria' for Starting Chronic Hemodialysis: Numbers, Symptoms or an Alerting 'Traffic Light' System? (Mustafa Arici, Ankara; Nephron Clin Pract 2012;120:c17-c24) Arici writes in this issue an "Opposite View" regarding the timing of starting renal replacement therapy (RRT). He cautions readers against the misinterpretation of recent data suggesting that late onset RRT is safe and that early initiation of dialysis can be harmful. He draws attention to the use of estimated GFR equations with their limitations and inaccuracies in CKD stage 5 as well as their misrepresentation of true GFR in wasted and sarcopenic CKD5 patients. He also stresses the importance of a more holistic approach to the initiation of RRT beyond a simple eGFR value. Finally, he makes the important distinction between late onset RRT and late referral of CKD4 and 5 patients. Suffice to say that in many emerging countries the great majority of those who start RRT are seen within 3 months from the onset of dialysis. The main question in my view is not when to start RRT, but instead when to refer patients with CKD3b and 4 to Nephrology centers to prepare for RRT. All too often the timing of referral is inappropriately late, thus being the main cause of poor outcomes.
Mechanism-Based Therapeutics for Autosomal Dominant Polycystic Kidney Disease: Recent Progress and Future Prospects (Chang and Ong, Sheffield; Nephron Clin Pract 2012;120:c25-c35) The authors provide readers with an up-to-date critical appraisal of mechanisms and treatment of autosomal dominant polycystic kidney disease (ADPKD). Lessons for nephrologists from the ADPKD story so far are: (1) translation from the laboratory to the bedside can, with concerted effort, take place relatively quickly in CKD, (2) animal models of disease do not always accurately reflect the human equivalent, and (3) biomarkers and surrogate markers of disease should not be the target of interventions; instead the hard endpoints of CKD progression and end-stage renal disease should be kept in focus. Finally, most clinical trials target a single ADPKD pathway. Perhaps progression in this condition will require a multitargeted approach. The ADPKD polypill combines a range of inhibitors of cell proliferation and transduction pathways: multitargeted therapy for a multigenetic disease?
Urinary Red Blood Cells: Not Only Glomerular or Nonglomerular (Poloni, Fogazzi and colleagues, Milan; Nephron Clin Pract 2012;120:c36-c41) This review reminds nephrologists of the lost art of urine microscopy. They go well beyond glomerular and non-glomerular hematuria as distinguished by the morphology and presence of dysmorphic urinary red blood cells. They describe urinary sickle cells, anisocytes, poikilocytes, dacryocytes and elliptocytes, and illustrate these urinary red blood cells' morphological alterations by the corresponding clinical conditions. The article reflects Professor Tita Fogazzi's passion for urine microscopy. He has turned urine microscopy into a rediscovered science and art. Practicing nephrologists, however, remain divided on the value of urine microscopy. Many hold it in high diagnostic esteem and some even raise it to the level of scientific art. Others, including myself, do not use urine microscopy for diagnostic purposes. I must confess that I have not looked at a single urine sediment in the last 25 years - whether this has affected my diagnostic ability may never be known!
Towards Erythropoietin Equations That Estimate Oxygen Delivery rather than Static Hemoglobin Targets (C.J. Diskin, Opelika, Ala.; Nephron Clin Pract 2012;120:c48-c53) The author argues that current inconsistencies in diagnosis and management may be the result of overlooking some basic physiological facts and the pathophysiology of anemia and oxygen delivery in CKD. Anemia in CKD is associated with changes in the oxygen-hemoglobin dissocation curve that is affected by variables such as acidosis, hyperphosphatemia as well as circulating/cellular urea levels. The review is a reminder to readers that simplistic therapeutic algorithms such as those currently in use for the management of anemia in CKD may cause more harm than benefit when they are not fully based on a better understanding of the pathophysiology of the underlying disease. Such understanding may become even more relevant when interventions to treat anemia of CKD are based on manipulations of hypoxia-inducible factors. Whether more complicated equations based on incorporating more modulators of anemia improve practice remains to be determined.