Juan Florencio Macias

Hematocrit, urea and gender: The Hematocrit, Urea and GEnder formula for prognosing progressive renal failure in diabetic nephropathy

OBJECTIVE Diabetic nephropathy is a common cause of end stage renal disease. Notwithstanding, wide inter-individual variations in the speed of progression of diabetic nephropathy are frequent. We have used the score of the HUGE formula to predict progression of kidney disease in a group of diabetic nephropathy patients. DESIGN AND METHODS The sample consisted of 84 type 2 diabetic patients. At treatment entry, the mean age was 62.1 ± 12.5 years and 59.5% were male. Blood pressure was measured at office at each visit. Serum creatinine, urea, hematocrit and 24h proteinuria were analyzed every 6 months. HUGE score was calculated from gender, urea and hematocrit. RESULTS Mean HUGE score was 0.99 ± 3.88. Using as cut off point 1.5, those patients who had a score equal or higher (n=31) showed a bigger increase in serum creatinine after one year (41.8 ± 62.1%) than those subjects with score<1.5 (n=53) (18.7 ± 38.6%, p=0.041). 5 patients with low HUGE score reached end stage renal failure (9.4%) and 10 patients in the high HUGE score group (32.3, p=0.008). When logistic regression analysis was performed only a HUGE score higher than 1.5 (p=0.003) and proteinuria higher than 2g/day (p=0.041) were independently associated to CRF progression (creatinine increment>25%). CONCLUSIONS In diabetic nephropathy patients the HUGE equation may be useful to detect the subjects prone to progressive renal failure. Wider samples will be needed to confirm this finding and, most important, its applicability to other kinds of nephropathy.

Beneficial effect of verapamil added to chronic ACE inhibitor treatment on renal function in hypertensive elderly patients.

This study analysed the effect of low doses ofverapamil added to chronic treatment withangiotensin-converting enzyme (ACE) inhibitors onblood pressure and serum creatinine levels in eightelderly hypertensive patients who had a steadyincrease of serum creatinine while on ACE inhibitors.The study was performed in eight elderly hypertensivesubjects, five men and three women (mean age 70 ±2 years; systolic blood pressure 173 ± 4 mmHg; diastolic blood pressure 99 ± 1 mm Hg) andserum creatinine of 1.60 ± 0.27 mg/dl beforetreatment. During an average of 25 weeks, ACEinhibitors significantly reduced both systolic anddiastolic blood pressures, but serum creatinine levelswere increased over basal levels (0,68 ± 0,20 mg/dl, p < 0.05). During an average of 10 weeks,the addition of verapamil did not decrease bloodpressure further, but serum creatinine levels werereduced to baseline. Our study suggests that theaddition of verapamil to ACE inhibitors can reverseACE-induced increase in creatinine levels in elderlyhypertensive patients in whom this side effect isobserved.

Hypertension in the elderly.

Data collected over a 30-year period have demonstrated the increasing prevalence of hypertension with age. Aging is an inevitable part of life and brings along two inconvenient events: physiologic decline and disease state. High blood pressure (HBP) is an important risk factor for cardiovascular morbidity and mortality, particularly in the elderly. It is a significant and often asymptomatic chronic disease, which requires optimal control and persistent adherence to prescribed medication to reduce the risks of cardiovascular, cerebrovascular and renal disease. Hypertension in the elderly patients represents a management dilemma to geriatric and cardiovascular specialists and other practitioners. Furthermore, with the wide adoption of multiple drug strategies targeting subgroups of hypertensive patients with specific risk conditions to lower blood pressure (BP), difficult questions arise about how aggressive treatment of elderly patients should be. The purpose of the following chapter article is to review the pathophysiology of aging as well as the epidemiology and the clinical assessment of high blood pressure (HBP) in older people.

Cardiovascular effects of elgodipine and nifedipine compared in anaesthetized rats

The cardiovascular effects of elgodipine were studied and compared with those of nifedipine in the presence or absence of ganglion blockade. A bolus of elgodipine (5-25 microg/kg) or nifedipine (60-120 microg/kg) was given and sequential cardiovascular effects in rats were recorded. Both dihydropyridines induced a dose-dependent decrease in mean arterial pressure but, whereas nifedipine induced reflex tachycardia, elgodipine induced a dose-dependent bradycardia. Both substances induced decreases in left ventricular d P/dt(max) without significant changes in central venous pressure. Good linear correlation was observed between the elgodipine-induced decrease in mean arterial pressure and those of heart rate and left ventricular dP/dt(max). The profile of the decrease in mean arterial pressure in animals pretreated with hexametonium chloride (20 mg/kg) was the same but the nifedipine-induced tachycardia was abolished without changes in elgodipine-induced bradycardia. These characteristics of elgodipine makes this dihydropyridine a potentially beneficial therapeutic agent in the case of severe hypertension accompanied by obstructive coronopathy.

Clinical Practice Guideline on management of older patients with chronic kidney disease stage 3b or higher (EGFR<45 mL/min/1.73 m2): A summary document from the European Renal Best Practice Group

The population of patients with moderate and severe CKD is growing. Frail and older patients comprise an increasing proportion. Many studies still exclude this group, so the evidence base is limited. In 2013 the advisory board of ERBP initiated, in collaboration with European Union of Geriatric Medicine Societies (EUGMS), the development of a guideline on the management of older patients with CKD stage 3b or higher (eGFR >45 mL/min/1.73 m2). The full guideline has recently been published and is freely available online and on the website of ERBP (www.european-renal-best-practice.org). This paper summarises main recommendations of the guideline and their underlying rationales.

Inhibition by nitrendipine of 86Rb+ fluxes in subconfluent MDCK cells.

Part of the natriuretic mechanism of dihydropyridine Ca2+ channel antagonists involves the inhibition of renal tubular sodium reabsorption. To identify the membrane ion transport system involved in this natriuretic action, we tested nitrendipine on unidirectional 86Rb+ fluxes in Madin-Darby canine kidney (MDCK) cells. To dissect between direct and indirect effects (via cytosolic Ca2+) of nitrendipine, the compound was re-examined on ion fluxes in human erythrocytes. In MDCK cells, external Ca2+ (3 mM), adrenalin (100 microM) and the Ca2+ ionophore A23187 (20 microM) strongly and transiently stimulated 86Rb+ efflux. All these stimulatory actions were fully inhibited by quinine (1 mM) suggesting that they reflect the opening of Ca(2+)-sensitive K+ channels. Nitrendipine was able to inhibit these Ca(2+)-sensitive K+ channels, bit this inhibitory action required concentrations of the compound (approximately 100 microM). Regarding 86Rb+ influx, the most significant result with nitrendipine was a partial inhibition of bumetanide-sensitive 86Rb+ influx. This effect represented a maximal flux inhibition of about 70% and required very low nitrendipine concentrations (IC50 approximately 1 nM). The Ca2+ ionophore A 23187 strongly stimulated bumetanide-sensitive 86Rb+ influx in MDCK cells. Conversely, a very important reduction (approximately 79%) of this influx component was found in Ca2+ depleted cells. In human red blood cells, Na+, K+, Cl- cotransport fluxes were resistant to nitrendipine, even at high concentrations of the compound (100-500 microM). Conversely, Ca(2+)-sensitive K+ channels were inhibited by nitrendipine with IC50 = 6 +/- 3 microM (mean +/- S.E.M., n = 3).(ABSTRACT TRUNCATED AT 250 WORDS)

Human NKCC2 cation–Cl– co-transporter complements lack of Vhc1 transporter in yeast vacuolar membranes

Cation–chloride co‐transporters serve to transport Cl– and alkali metal cations. Whereas a large family of these exists in higher eukaryotes, yeasts only possess one cation–chloride co‐transporter, Vhc1, localized to the vacuolar membrane. In this study, the human cation–chloride co‐transporter NKCC2 complemented the phenotype of VHC1 deletion in Saccharomyces cerevisiae and its activity controlled the growth of salt‐sensitive yeast cells in the presence of high KCl, NaCl and LiCl. A S. cerevisiae mutant lacking plasma‐membrane alkali–metal cation exporters Nha1 and Ena1‐5 and the vacuolar cation–chloride co‐transporter Vhc1 is highly sensitive to increased concentrations of alkali–metal cations, and it proved to be a suitable model for characterizing the substrate specificity and transport activity of human wild‐type and mutated cation–chloride co‐transporters. Copyright

Lercanidipine valuable effect on urine protein losses: the RED LEVEL study

Abstract Objective: The RED LEVEL study (REnal Disease: LErcanidipine Valuable Effect on urine protein Losses) directly compares, in an explorative fashion, the effects of lercanidipine + enalapril and amlodipine + enalapril combinations on renal parameters in hypertensive subjects. Research design and methods: This was a 1 year, prospective, multi-center, randomized, open-label, blinded-endpoint (PROBE) study in hypertensive patients with albuminuria. Main outcome measures: Renal function (albuminuria, serum creatinine, creatinine clearance, estimated glomerular filtration rate and proteinuria); blood pressure. Results: Albuminuria was significantly reduced, compared with baseline values, with the lercanidipine + enalapril combination over the entire study period; at month 3, month 6 and month 12, changes from baseline were: −162.5 (p-value = 0.0439), −425.8 (p-value = 0.0010), −329.0 (p-value = 0.0011) mg/24 h), respectively. On the other hand, this improvement was not observed with enalapril + amlodipine. Other parameters of renal function such as serum creatinine, creatinine clearance, estimated glomerular filtration rate and proteinuria did not change over the study. Both lercanidipine + enalapril and amlodipine + enalapril significantly reduced systolic and diastolic blood pressure values from baseline all over the study period with no significant differences between groups. Safety outcomes were comparable between the two groups. Conclusions: Overall, the results of this explorative study lend support to the anti-albuminuric effect of the lercanidipine + enalapril combination and to the long term renal-protective effects of this combination in patients with hypertension.

A proposal for improving the KDIGO renal disease risk table.

Recent surveys have revealed that the prevalence of chronic kidney disease (CKD), particularly the hidden mild form (mildly elevated levels of serum creatinine or urinary albumin excretion), is surprisingly high in the general population. In recent years, the global epidemic of type-2 diabetes has led to an alarming increase in the number of patients with CKD. Most patients with CKD (over 50 million individuals worldwide) succumb to cardiovascular events, while each year over 1 million develop end-stage renal failure, which requires costly treatment and in many countries of the world, unaffordable renal replacement therapy by chronic dialysis or renal transplantation [1]. The diagnosis and management of CKD has been made easier in recent years by the Kidney Disease Outcomes Quality Initiative (K/DOQI) clinical practice guidelines of the US National Kidney Foundation. The K/DOQI guidelines advise that CKD can be defined and appropriately managed by a staging approach that relies on estimating the severity of kidney damage based on the degree of proteinuria and impaired kidney function, the latter assessed as a decrease in the glomerular filtration rate (GFR). CKD is defined as kidney damage for [3 months, with or without decreased GFR, manifested by either pathologic abnormalities or markers of kidney damage such as proteinuria 3.4. If there are no signs of kidney damage, a diagnosis of CKD cannot be made until the GFR is\60 mL/min/1.73 m [2]. Using this standard of measure, the National Kidney Foundation estimates that 20 million Americans have CKD, while an additional 20 million are at risk of the disease [3]. During this time, an increasing recognition has emerged about the definition and classification limitations, leading to a heated debate and calls for revisions, mainly in nephrology subspecialty journals. The leadership of KDIGO (Kidney Disease: Improving Global Outcomes), with the endorsement of K/DOQI, convened a Controversies Conference to provide a forum for an open discussion on this problem [4]. One important issue was whether or not the current classification (based on eGFR) should be modified to include additional factors associated with prognosis. The conference generated a table similar to the one used for the European Hypertension Guidelines [5]. It was drawn by a composite ranking of relative risks that enhances communication about prognosis in which colours indicate groups of patients at progressively higher risk for the major outcomes. This table (Fig. 1) would help clinicians, researchers and public health agencies to describe and prioritise efforts aimed at patients and populations at risk of renal disease. The main improvement in the table is to add the value of urinary albumin excretion categorised by N. R. Robles J. F. Macias J. Alvarez-Gregori Cardiovascular Risk Chair, University of Salamanca School of Medicine, Salamanca, Spain