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ISSN: 0975-766X CODEN: IJPTFI Available Online through Research Article www.ijptonline.com A STUDY OF AUTONOMIC NEUROPATHY IN PATIENTSOF CHRONIC RENAL FAILURE Venugopala. D *1, Sahil. K, Shyamala. K.V *2 Department of medicine,kasturba Medical college,mangalore,manipal University,-575001,India Department of Physiology,Kasturba Medical College,Mangalore,Manipal University,-575001,India Email:drshyamala@live.com Received on 16-07-2013 Accepted on 31-07-2013 Abstract: Several abnormalities in cardiovascular autonomic function have been found in chronic renal failure patients and it is associated with increase in mortality in these patients. So the study of autonomic neuropathy in patients of chronic renal failure was taken up. Methods: A study was done on clinical profiles of autonomic neuropathy in patients of chronic renal failure patients. Detailed clinical history, a thorough clinical examination, lab investigations and the following clinical tests for autonomic neuropathy were done. Heart rate variability in response to deep breathing, heart rate variability in response to standing, heart rate in response to Valsalva maneuver, blood pressure response to standing and BP response to sustained hand grip exercise were recorded. Values obtained from the various tests were tabulated into a worksheet. Result: Out of 100 patients, maximum numbers of patients belong to the age group of 50 60 years. In 43% of the chronic kidney disease patients the main cause was diabetes, while in 21% patients the important cause was hypertension. Symptoms suggestive of autonomic neuropathy were present in 64% patients. 42% patients had evidence of autonomic neuropathy.58.1% of them were diabetic patients and 29.8% of them were nondiabetic patients. Conclusion: Diabetes mellitus was the commonest etiology for chronic renal failure followed by hypertension and obstructive uropathy.autonomic neuropathy is well associated with chronic renal failure patients. Knowledge of autonomic dysfunction canencourage patients and physicians to improve metabolic control. Key words: Autonomic neuropathy chronic renal failure mortality diabetes mellitus hypertension. Introduction Chronic Renal Failure (CRF) is a pathophysiologic process with multiple etiologies, resulting in an irreversible attrition of nephron number and function. Central, peripheral and autonomic neuropathies are common complications of CRF. IJPT July-2013 Vol. 5 Issue No.2 5536-5542 Page 5536

Several abnormalities in cardiovascular autonomic function have been found in CRF patients. Its early recognition remains a challenge. This is mainly because it does not have any pathognomonic symptoms. Patients develop symptoms late in the course of the disease. Symptoms of uremic neuromuscular disease do not manifest until beginning of stage 3 CRF. 1 It may have a number of clinical sequealae, but the pathogenesis is unknown. 2,3,4 Clinical symptoms of autonomic neuropathy, such as gustatory sweating, and those related to enteropathy, cystopathy and orthostatic hypotension are rare. On the other hand asymptomatic abnormalities are not uncommon after 10-15 years' duration of chronic kidney disease. 5 Clinically,the impairment in autonomic function causes exercise intolerance and orthostatic hypotension. 6 In recent years there has been a growing interest in the cardiovascular autonomic neuropathy in chronic renal failure because of its association with increase in mortality in these patients. So thestudy of autonomic neuropathy in patients of chronic renal failure was taken up. Materials and methods A prospective study was done in KMC associated hospitals from June 2010 to February 2011 on clinical profiles of autonomic neuropathy in patients of chronic renal failure were taken up. Inclusion criteria: All patients of 15-60 years meeting the criteria of chronic renal failureas defined by National kidney foundation 7. Exclusion criteria: Patients who are on drugs that affect autonomic nervous system like beta blockers, catecholamineetc.,patients having neurological diseases that affect autonomic system like cerebrovascular accidents etc., patients who have severe illness of other systems e.g. CCF, respiratory failure and the patients who are moribund and cannot perform valsalva manoeuvre. 100patients meeting the inclusion criteria were evaluated in detail. The evaluation comprised of detailed clinical history, a thorough clinical examination, lab investigations and the following clinical tests for autonomic neuropathy were done. Heart rate variability in response to deep breathing, heart rate variability in response to standing heart rate in response to valsalva maneuver, blood pressure response to standing and BP response to sustained hand grip exercise were recorded. Values obtained from the various tests were tabulated into a worksheet and a scoring system was applied to each test as recommended by Bellavereet al. 8 IJPT July-2013 Vol. 5 Issue No.2 5536-5542 Page 5537

Table1: Age&sex distribution: Shyamala. K.V* et al. International Journal Of Pharmacy & Technology Age group(in years) Males Females <40 8 7 40-50 9 6 50-60 30 20 >60 11 9 Table11: Etiology of Chronic kidney diseases: Etiology(diagnosis) No of patients Diabetes Mellitus 43 Hypertension 21 Chronic Glomerulonephritis 7 Idiopathic 7 Obstructive Nephropathy 13 Others 9 Table111: Distribution of patients with various autonomic dysfunction symptoms: Symptom No. of patients Cardio vascular 43 Urological 29 Gastrointestinal 39 IJPT July-2013 Vol. 5 Issue No.2 5536-5542 Page 5538

Table1V: Percentage distribution of Autonomic neuropathy in chronic renal failure: Types Total no. of No. of patients with Pecentage patients autonomic neuropathy Diabetic patients 43 25 58.1 Non diabetic patients 57 17 29.8 Table V: Percentage distribution of sex in autonomic neuropathy: Sex Total no. of patients No of patients with autonomic Percentage neuropathy Males 58 28 48.27 Females 42 14 33.33 Out of 100 patients, 58 were males and 42 were females. The mean age was 51.28 yrs. The youngest patient was 19 year old and the oldest was 66 years old. Maximum numbers of patients belong to the age group of 50 60 years. In 43% of the chronic kidney disease patients the cause was diabetes, while in 21% patients the cause was hypertension; 13% the cause was obstructive uropathy; 7% patients had chronic glomerulonephritis and 7% patients had idiopathic CKD. 4 patients had polycystic kidney disease as the cause of CKD. 2 patients had Multiple myeloma. One had drug induced CKD, while one patient had chronic interstitial nephritis and another one patient had membranous nephropathy. Symptoms suggestive of autonomic neuropathy were present in 64% patients. 43% had CVS symptoms in the form of postural giddiness and palpitations. 39% had GIT symptoms in the form of post prandial bloating sensation and nocturnal diarrhea 29% of patients had Genito-urinary symptoms which were seen predominantly in males. Sudomotor symptoms were seen in 10 % of cases.42% patients had evidence of autonomic neuropathy.58.1% of them were diabetic patientsand 29.8% of them were non-diabetic patients.48.27% of the male patients had autonomic neuropathy whereas 33.33% of females had autonomic neuropathy. IJPT July-2013 Vol. 5 Issue No.2 5536-5542 Page 5539

Discussion Shyamala. K.V* et al. International Journal Of Pharmacy & Technology In our study (table1) autonomic dysfunction is more prevalent in males than females.agarwala,vita Get al and Calvo C et al also got the similar findings in their study on autonomic dysfunction in CRF patients 9,10,11 Vita G et al in their study of autonomic neuropathy in chronic uremic patients found the mean age of patients was 48. 12 Laaksonen S et al in their study of autonomic nervous system abnormalities in CRF patients found the mean age as 52.3 years 13 which is more likely to our study. But Calvo C et al in their study found slightly lesser aged people compared to our study. Diabetes mellitus was the commonest etiology followed by hypertension and obstructive uropathy(table11)in our study. Sanya EO et al in their study found diabetes as the commonest cause for CKD followed by chronic glomerulonephritis. 14 Aggarwal A et al in their study found diabetes and obstructive nephropathy as the leading cause of CKD. 9 A study on CRF patients carried out in Nigerian population cardiovascular autonomic neuropathy was a common complication. 15 Similar findings were seen in our study also. (table111). As shown in table1v 58.1% of patients who had evidence of autonomic neuropathy were diabetics. In randomly selected cohorts study on asymptomatic individuals with diabetes 20% had abnormal cardiovascular autonomic function. 16 One of the most overlooked of all serious complications of diabetes iscardiovascular autonomic neuropathy.62% of males&38% of females had autonomic neuropathy in CRF patients. 17 Similar to this in our study also48.27% of the male patients and 33.33% of females had autonomic neuropathy (table V).So autonomic neuropathy is well associated with chronic renal failure patients. Knowledge of autonomic dysfunction canencourage patients and physicians to improve metabolic control. References: 1. Agaba EI, Tzamaloukas AH. Neurological manifestations of uraemia. Niger J Med. 2004; 13(2): 98 105. 2. Langer A, Freeman Mr, Josse RG, Armstong Pw, Metaiodobenzylguanidene imaging in diabetes mellitus: assessment of cardiac sympathetic denervation and its relation to autonomic dysfunction and silent myocardial ischemia. J Am CollCardiol 1995; 25: 610-618. IJPT July-2013 Vol. 5 Issue No.2 5536-5542 Page 5540

3. Campese VM, Romoff MS, Levitan D, Lane K &Massry SG. Mechanisms of autonomic nervous system dysfunction in uremia. Kidney Int 1981; 20: 246 253. 4. Heidbreder E, Schafferhans K &Heidland A. Autonomic neuropathy in chronic renal insufficiency: Comparative analysis of diabetic and non-diabetic patients. Nephron 1985; 41: 50 56. 5. Bennett T, Hosking DJ, Hampton JR. Cardiovascular control in chronic renal failure. Br Med J II. 1975; 585-587. 6. Weimer LH,Autonomic function.in.evansrw.diagnostic testing in neurology.pennysylvaniia:w.b Saunders Company; 1999:337-365. 7. Winney, Vita J. Definition of chronic renal failure: Brenner and Rector sthe Kidney, Vol. 1, 6 th Ed. 2000: 1088 1089. 8. Bellavere F, Balzani I, De Masi G, Carraro M, Carenza P, Cobelli C &Thomaseth K. Power spectral analysis of heart-rate variations improves assessment of diabetic cardiac autonomic neuropathy. Diabetes 1992; 41: 633 640. 9..Agarwal A, Anand IS, Sakhuja V &Chugh KS. Effect of dialysis and renal transplantation on autonomic dysfunction in chronic renal failure. Kidney Int 1991; 40: 489 495. 10. Vita G, Princi P, Calabrò R, Toscano A, Manna L & Messina C. Cardiovascular reflex tests: Assessment of ageadjusted normal range. J NeurolSci 1986; 75: 263 274. 11. Calvo C, Milone S, Trusso A, Bellinghieri G & Messina C. Uremic autonomic neuropathy:clinical tests. ClinNephrol 1999; 65: 76 80. 12. Vita G, Princi P & Messina C. Multivariate analysis of cardiovascular reflexes applied to the diagnosis of autonomic neuropathy. J Neurol 1991; 238: 251 255. 13. Laaksonen S, Malfatto G, Masu AM, Poli M, Guzzetti S, Lombardi F, Cerutti S &Malliani A. 54.Spectral analysis of heart rate variability in the assessment of autonomic diabetic neuropathy. J AutonNervSyst 1988; 23: 143 153. 14. Sanya E O, Wieling W &Mancia G. Blood pressure and heart rate variability in autonomic disorders: A critical review. ClinAuton Res 1996; 6: 171 182. 15. SanyaEO,OgumiyiA.Cardivascular autonomic neuropathy in non-diabetic Nigerian patients with chronic renal failure patients.wajm2004;23:89-94 IJPT July-2013 Vol. 5 Issue No.2 5536-5542 Page 5541

16. AoronIV,DanZieger.Diabetic. cardiovascular autonomic neuropathy.circulation J2007;115:387-397. 17. Carmine Z,FrancescaM,Giovani et al.autonomic Neuropathy is linked to nocturnal hypoxaemia and to concentric hypertrophy and remodeling in dialysis patients. Nephrol Dial Transplant. 2001; 16:70-77. Corresponding Author: Shyamala. K.V * Email:drshyamala@live.com IJPT July-2013 Vol. 5 Issue No.2 5536-5542 Page 5542