The purpose of this study was to examine proximal and distal tubular function in rats with nonoliguric, myohemoglobinuric acute renal failure (ARF). ARF was induced with glycerol (50%, 10 ml/kg of body wt, i.m.), and renal function was studied 24 hours after glycerol or saline (controls) injection. Glycerol injection caused a 50 to 90% depression in GFR and a significant rise in blood urea nitrogen concentration. Animals with ARF exhibited glycosuria with normal blood sugar levels and a striking depression in tubular glucose reabsorption per milliliter of GFR. The capacity to reabsorb (mEq/liter GFR) was intact at normal blood bicarbonate levels, but was markedly depressed when blood bicarbonate was raised. The tubular maximum for para-aminohippurate (PAH) secretion and the renal extraction fraction of PAH were strikingly depressed in rats with ARF. Distal acidification as assessed by the urine-to-blood gradient of PCO2 (UB PCO2) was normal both during maximal alkalinization of the urine with bicarbonate (urine pH, approximately 7.8) or during neural phosphate infusion (urine pH, approximately 7.0). Net acid excretion per milliliter GFR and minimal urine pH (less than 5.5) following 3 days of ammonium chloride ingestion was similar in control and ARF animals. Potassium excretion was intact in maximal urinary osmolality were significantly altered in animals with ARF. Cortical and outer medullary Na-K-ATPase specific activities were significantly depressed in ARF rats. This occurred as a consequence of enzyme loss and not secondary to alterations in enzyme kinetics of absolute tubular sodium reabsorption. Light and electron microscopy showed diffuse proximal tubular damage, whereas glomeruli and distal tubules were intact. These data demonstrate that glycerol injection produces a diffuse proximal tubular transport defect associated with histologic and enzymatic alterations.

To evaluate the mechanism responsible for the effect of deoxycorticosterone acetate (DOCA) on renal Na+-K+-ATPase, we compared the relative contribution of this hormone and of increased absolute sodium reabsorption (TNa) to the restoration of the enzyme in kidneys of adrenalectomized rats. In study A, adrenalectomized animals maintained on a salt-free diet received 5 mg/kg per day DOCA i.m., while sham-operated and untreated adrenalectomized rats receiving the same diet served as controls. Absolute TNa and Na+-K+-ATPase specific activity in the cortex and outer medulla of DOCA-treated rats were similar to those measured in untreated adrenalectomized animals, but were significantly lower than in sham-operated controls. In study B, the adrenalectomized rats did not receive DOCA but were fed a high salt diet and received isotonic saline, 50 ml/kg per day s.c. Absolute TNa and cortical and medullary Na+-K+-ATPase specific activity were significantly higher in the salt-loaded group than in both adrenalectomized and sham-operated rats deprived of salt. These results suggest that absolute sodium reabsorption is a major determinant of renal Na+-K+-ATPase activity, and that the effect of DOCA on this enzyme is secondary to its stimulation of absolute tubular sodium transport.

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Background and Aims Chronic kidney disease (CKD) has been proposed as a model of premature ageing. The immune system is an important factor in the ageing process and can modulate the rate of ageing. The uremic environment highly affects this system, deteriorating its functionality and increasing susceptibility to infections, cancer, and pathologies like cardiovascular disease. Also, CKD patients are highly predisposed to frailty, which increases the organism's vulnerability to disease. This premature ageing, partially caused by the immune disorder and increased frailty, is responsible for these patients' high morbidity and mortality. Understanding these processes and how they are affected by different treatments will help generate better nutritional, pharmacological and lifestyle strategies. For this, the aim of this study was to determine the immune and frailty status of patients with CKD and their therapies. Method We performed a cross-sectional study involving 18 healthy subjects (HS) and 156 patients from the Nephrology Department of the Hospital Universitario “12 de Octubre” (Madrid, Spain). The distribution of patients was as follows: 40 with end-stage renal disease (ESRD), 40 on haemodialysis (HD), 36 on peritoneal dialysis (PD) and 40 patients who had received initial kidney transplantation (KT). The frailty status of the patients was assessed by the Edmonton Frail Scale test. Lymphocyte populations (T lymphocytes, T-helper lymphocytes, T-cytotoxic lymphocytes, and B lymphocytes) and monocytes (classical, intermediate, non-classical, and the expression of the adhesion molecule ICAM-1 and co-stimulatory B7.2) were determined in peripheral blood samples. Results The patients were similar in age and sex. The number of frail individuals was higher in patients (ESRD p<0.001, PD p<0.001, KT p = 0.004) than in HS, particularly in HD (p<0.001) (Figure 1). Regarding immune phenotype (Figure 2), HD patients showed a lower number of T-cells (p<0.001), particularly T-helper cells (p<0.001), than the other groups. Also, DP patients presented fewer T and T-cytotoxic cells than HS (p = 0.029, p = 0.05). Also, HD showed lower T-cytotoxic and helper/cytotoxic ratios than HS (p = 0.022; p = 0.011) and ESRD (p = 0.017; p = 0.008). The proportion of classical monocytes decreased, and the proportion of intermediate and non-classical monocytes increased in HD with respect to the other groups (p<0.001). The expression of the costimulatory molecule B7.2 was increased in the patients with respect to HS in all monocyte subsets (Classical: ESRD p = 0.002, HD p<0.001, PD p<0.001, KT p<0.001; Intermediate: ESRD p = 0.014, HD p<0.001, PD p<0.001, KT p = 0.002; Non-classical: ESRD p = 0.006, HD p<0.001, PD p<0.001, KT p = 0.013), while adhesion molecules were only elevated in HD with respect to HS in all subsets (classical p<0.001, intermediate p<0.001, non-classical p = 0.023). Conclusion The CKD patients, regardless of the treatment, showed, in general, an alteration in the lymphocyte subsets. These alterations were more significant in dialysis patients, particularly in HD patients. This group also presented the most significant alterations in monocyte subsets and higher frailty. This may explain why haemodialysis patients show major adverse outcomes compared to other treatments. Determining immune profiles can help us to relate these alterations to adverse events to carry out preventive and personalised medicine.