Blog entry by Meguid El Nahas

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by Meguid El Nahas - Friday, 11 March 2011, 8:12 PM
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Albumin:Creatinine Ratio - A Flawed Measure. The Merits of Estimated Albuminuria Reporting (Tim Ellam, Sheffield; Nephron Clin Pract 2011;118:c324-c330) Ellam presents the Opposite View to the fact that urine Albumin:Creatinine Ratio (ACR) is a reliable indicator of urinary albumin excretion. He reminds the reader of the limitations of this calculation and the fact that confounders of urine creatinine excretion are seldom considered. For instance, a low urinary excretion of creatinine may reflect muscle wasting and ill health, thus raising ACR in the absence of changes in urine albumin excretion. Low urinary creatinine excretion, like that of albumin, is known to be associated with CVD and increased mortality, thus confoundingthe prognostic significance of a raised ACR. The author argues that urinary creatinine excretion needs to be adjusted for key confounders such as age, gender, race and muscle mass. This, in fact, has been recently suggested by Ix and colleagues (Clin J Am Soc Nephrol 2011;6:184-191) who have put forward urine creatinine excretion formulas that adjust for gender and age. So beware Nephrologists when you use ACR/PCR to bear in mind such important confounders; after all, they are the same that justified formulations that include age, gender and race for adjustments in serum creatinine measurements and eGFR calculations.


Proteinuria in Type 2 Diabetic Patients with Renal Impairment: The Changing Face of Diabetic Nephropathy (Packham and colleagues on behalf of the collaborative study group, Melbourne, Chicago, Ill., Nashville, Tenn., and Groningen; Nephron Clin Pract 2011;118:c331-c338) The authors note that over one fifth of patients with type 2 diabetic nephropathy and established renal impairment have proteinuria levels below those traditionally associated with overt nephropathy. They attribute this to the likelihood that these patients are receiving ACEis, ARBs, or a combination of both. Another important consideration is that the type of patients with so-called diabetic nephropathy has been changing since the early days of description of the natural history of diabetic nephropathy by Mogensen et al. (Scand J Clin Lab Invest 1976;36:383-388) in the seventies!? Those were predominantly younger patients with progressive nephropathy and heavy proteinuria, which was the rationale behind ACEis. Nowadays, the patients we see are older, with type2 diabetes mellitus and often suffer from longstanding hypertension preceding the diagnosis of diabetes mellitus by years. They often have diffuse and severe atherosclerosis with consequent renovascular disease and ischemic nephropathy. Proteinuria in these patients is mild to moderate and progression slow. ACEi, ARB or a combination of both is likely to be harmful (see results of the ONTARGET study, Lancet 2008;372:547-553). It is high time Nephrologists reconsider the use of ACEis/ARBs in such patients. Some have even stopped them in advanced nephropathy in patients with diabetes to good effects (Ahmed et al., Nephrol Dial Transplant 2010;25:3977-3982).


Treatment of HIV-Associated Nephropathies (Elewa and colleagues, Cairo, Porto Alegre and Rochester, Minn.; Nephron Clin Pract 2011;118:c346-c354) This review highlights a number of new and important issues including the perceived increased prevalence of CKD in HIV-infected individuals and the association with known predisposing factors such as the black race, low CD4 count, high HIV RNA copies level, but also new and interesting risk factors such as a family history of CKD and the presence of diabetes mellitus, hypertension or hepatitis C co-infection. In emerging countries/regions where HIV prevalence is high, CKD is likely to result from the triple hit of poverty, infections and westernization with increased incidence of hypertension and diabetes. Also, additional environmental or inherited factors may be necessary to initiate human HIVAN. Elewa and his colleagues remind us that the evidence upon which HAART treatment recommendations is based is weak. A recent search involving the Cochrane Central Register of Controlled Trials (CENTRAL) found no RCT-based evidence upon which to base guidelines for the treatment of HIVAN. Clearly, more research is needed to understand HIVAN, its epidemiology, classification and treatment.


Metformin: The Safest Hypoglycaemic Agent in Chronic Kidney Disease (Nye and  Herrington, Oxford; Nephron Clin Pract 2011;118:c380-c383). The authors remind the reader that lactic acidosis following treatment of patients with diabetic nephropathy with metformin is rare and unpredictable. It is usually precipitated by an additional acute condition predisposing to tissue hypoxia. Metformin is an effective oral agent in the treatment of type 2 diabetes and in the prevention of its complications, particularly in overweight patients. Although a number of reports have been published suggesting that metformin is a cause of lactic acidosis, a systematic review of all the available trials and cohort studies does not support this. In fact, the evidence suggests that type 2 diabetes mellitus itself may be associated with reduced lactate clearance and may be a more important risk factor for lactic acidosis than metformin.

We should be cautious not to deprive our diabetic patients from an excellent drug on the basis of a poor understanding of the published literature. This is one more proof that we seldom read the evidence upon which we base our practices; withdrawal of metformin in patients with a serum creatinine>150 micromol/l!? One would hope that those who draft guidelines do...?!

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