Effects of graded exercise training on functional capacity, muscle strength, and fatigue after renal transplantation: a randomized controlled trial.

Successful renal transplantation (RT) recipients suffer residual muscle weakness, fatigue, and low functional capacity. A safe, feasible, structured, early graded exercise training to improve functional capacity, muscle strength, and fatigue is the need of the hour. The aim of the study is to assess the effectiveness of graded exercise training on the functional capacity, muscle strength, and fatigue after RT. It is a randomized controlled trial conducted at a tertiary care hospital from January 2012 to December 2016. This trial included 104 consented, stable renal transplant recipients without cardiopulmonary/neuromuscular impairment. They received either routine care (51) or graded exercise training (53) for 12 weeks after randomization. The functional capacity, isometric quadriceps muscle strength, and fatigue score were measured at baseline, six, and 12 weeks later to induction. The outcomes of the study and control groups were analyzed using the /-test, Wilcoxon signed-rank test, ANOVA, and Pearson's correlation. For all analyses, P <0.05 was fixed acceptable. The functional capacity improved by 147 and 255 m, the muscle strength by 6.35 and 9.27 kg, and fatigue score by 0.784 and 1.781 in the control and the study group (SG), respectively, significantly more in the SG. Functional capacity had a positive and negative correlation with muscle strength and fatigue, respectively (P <0.05). The graded exercise training significantly improved the functional capacity, fatigue levels, and muscle strength after RT.

Angiotensinogen gene polymorphisms and progression of chronic kidney disease in ADPKD patients.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a multisystemic and progressive disorder characterized by cyst formation and kidney enlargement and ultimately renal failure. Reduction of CKD progression in the ADPKD by pharmacological blockade of the renin-angiotensin-aldosterone system (RAAS) using ACE inhibitors indicated the involvement of RAAS pathway in the progression of CKD. The aim of the present study is to investigate the role of angiotensinogen tag-single nucleotide polymorphisms (AGT tag-SNPs) in progression of CKD. METHODS: Twelve AGT tag-SNPs were genotyped in 102 ADPKD patients and 106 non-ADPKD subjects using FRET-based KASPar method. Genotypes and haplotypes were compared between ADPKD and controls. The effect of genotypes and hypertension on CKD progression was assessed using univariate and multivariate logistic regression. Mantel-Haenszel (M-H) stratified analysis was performed to study the interaction between CKD stages and hypertension. RESULTS: Of the twelve tag-SNPs analyzed, only rs11122578 SNP deviated Hardy-Weinberg equilibrium in controls. Significant association between two AGT polymorphisms (rs11122577 and rs4762) and ADPKD was observed. Analysis of linkage disequilibrium revealed two haplotype blocks and haplotypes are not associated with ADPKD. The univariate analysis revealed that the age, hypertension, family history of diabetes and AGT rs4762 contributed to the progression of CKD in ADPKD. The modifier effect of these factors remained even after controlling other variables in multivariate analysis. CONCLUSIONS: The results of our study suggest significant association between Thr207Met polymorphism of AGT and CKD progression and acts as an effect modifier of renal disease progression in ADPKD.

Role of the ACE ID and PPARG P12A Polymorphisms in Genetic Susceptibility of Diabetic Nephropathy in a South Indian Population.

BACKGROUND: Diabetic nephropathy (DN) is one of the life-threatening disorders characterized by persistent albuminuria, raised arterial blood pressure, a lowered glomerular filtration rate, and high risk of cardiovascular morbidity and mortality. The vascular genes ACE (Angiotensin-converting enzyme), and PPARG (peroxisome proliferator activated receptor gamma) are involved in alterations in vascular endothelium, and are suggested to play a role in the susceptibility of diabetic nephropathy. OBJECTIVES: The aim of our study was to find out the role of ACE ID and PPARG P12A polymorphisms in genetic susceptibility of diabetic nephropathy in south Indian population. PATIENTS AND METHODS: A total of 54 cases with diabetic nephropathy and 67 control subjects with diabetes were enrolled for our study. DNA was isolated from peripheral blood leucocytes, and genotyped using PCR-electrophoresis (ACE ID) or PCR-RFLP (PPARG P12A) methods. RESULTS: ACE ID genotypes followed Hardy-Weinberg equilibrium in both cases and controls. But P12A genotypes deviated from Hardy-Weinberg equilibrium in diabetic controls. Chi(2) test was applied for the analysis of genotypic distributions in genotypic and dominant models. Odds ratios were also calculated. No significant differences in genotype frequencies of ACE ID and PPARG P12A polymorphisms were found on comparing patients with diabetic nephropathy with diabetic controls. The synergistic role of ACE ID* PPARG P12A interaction, did not show any association in patients with diabetic nephropathy when compared to diabetic controls. CONCLUSIONS: In conclusion, the ACE and PPARG genes do not have a key role in conferring risk for diabetic nephropathy.

Hemodialysis: a therapeutic option for severe attacks of acute intermittent porphyria in developing countries.

Acute intermittent prophyria (AIP) is an autosomal dominant disease that results from a defect in the enzyme porphobilinogen deaminase. Acute intermittent porphyria is the most common of hepatic porphyrias and can tax the therapeutic capabilities of the physician to the limit. Motor weakness is a major feature of an acute attack, and flaccid paralysis of all extremities can occur rapidly, within a matter of days. The acute attacks may be life threatening. Hematin (Heme Arginate) should be given early during an acute attack to prevent neurologic sequel. Hemodialysis and hemoperfusion have been tried in the treatment of acute attacks of AIP with success. As hematin is not available in India, a severe acute attack of AIP in a patient was managed with hemodialysis successfully. Later, hematin was imported and provided to the patient. An 18-year-old girl was admitted to our hospital with recurrent abdominal pain and 2 episodes of convulsions. She had undergone an appendectomy earlier at another hospital for abdominal pain. On evaluation, she had hyponatremia, episodic abnormal behavior, generalized muscle pain, hypertension, and sinus tachycardia. In view of the above clinical picture, a clinical diagnosis of acute intermittent porphyria was made. Her 24-hr urinary porphobilinogen was 90.8 mg/day (<2 mg-normal) and alpha amino levalunic acid was 108.8 mg/day (1-7 mg-normal), consistent with the diagnosis. Her hyponatremia was corrected. Arrangements were made to import hematin and she was managed with dextrose infusion. Meanwhile, she developed flaccid quardriparesis with urinary incontinence and bulbar palsy. Her brain MRI was normal. Her nerve conduction study was suggestive of motor radiculoneuropathy. Specific treatment for severe porphyric crisis was planned. She failed to improve with dextrose infusion alone. As hematin was not readily available in the country, other therapeutic options were considered. As few case reports of AIP being successfully treated with hemodialysis were available, the option of dialytic support was explained to the family. After procuring informed consent, she was subjected to hemodialysis for 4 hr in the first day, increasing to 6 hr a day for the next 6 days. Her abdominal pain and myalgia subsided on the third day of dialysis. Her lower limb muscle power improved and she became ambulant by the fourth day. Urinary retention improved within 4 days. Hematin was imported by then from the United States. Later, 2 doses of hematin (4 mg/kg-160 mg in 20% albumin) were given via a central vein. She was maintained on physiotherapy. Repeat nerve conduction study revealed recovery. She has been provided with a list of drugs that have to be avoided. Currently, she is on outpatient follow-up with occasional abdominal pain, which subsides with intravenous dextrose therapy.