PREVALENCE AND PATTERNS OF HYPERPARATHYROIDISM AND MINERAL BONE DISEASE IN PATIENTS WITH CHRONIC KIDNEY DISEASE AT KENYATTA NATIONAL HOSPITAL

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1 PREVALENCE AND PATTERNS OF HYPERPARATHYROIDISM AND MINERAL BONE DISEASE IN PATIENTS WITH CHRONIC KIDNEY DISEASE AT KENYATTA NATIONAL HOSPITAL DR. ANNE MUGERA

2 The Problem Chronic Kidney disease is a worldwide epidemic- over 1.1mil in CKD stage 5 Growth rate of 6%-8% per annum of dialysis patients

3 Epidemiology ESRD- >2000 per million population in Japan, 1500/million in the US, 800/million in EU.?CKD 3-4 more frequent amongst Africans, than developed countries. However; Incidence of CKD in Africa is unknown No reliable statistics of Morbidity & Mortality of CKD incl Kenya? Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030.Diabetes Care 2004;27: International Society of Nephrology. Program for detection and management of chronic kidney disease, hypertension, diabetes, and cardiovascular disease in developing countries (KHDC). (Accessed February 17, 2006,

4 The Problem-Mortality in CKD Rizwan A Hamer et al, The burden of chronic kidney disease BMJ 2006;332: (11 March); Foley RN, Parfrey PS, Sarnak MJ. Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis1998; 32

5 Complications of CKD Cardiovascular disease Anemia Abnormalities of mineral metabolism (PTH, Ca,Phos) Reduced quality of life/physical well being.

6 CKD stage and changes in Mineral Metabolism Increases in ipth preceded changes in serum Ca and P.

7 Pathophysiology of Secondary Hyperparathyroidism

8 Impact(consequences) of SHPT Mineral Bone Disease(MBD)- Renal Osteodystrophy High turn over bone disease osteitis fibrosa cystica- PTH levels = oteoclast stimulation= bone resorption Low turn over bone disease Osteomalacia Low turn over Adynamic bone disease Extraskeletal calcifications (calciphylaxis in CVS) Endocrine disturbances (EPO, RAS)

9 Intact PTH and mortality

10 Renal Osteodystrophy(CKD-MBD

11 Bone Metabolism and CVD

12 Utility of Biochemical Markers

13 Justification CKD worldwide public health problem Severity of secondary HPT correlates directly with increased morbidity and mortality (esp in the dialysis population.) Data on American/European population, may not necessarily apply to the African population Prompt recognition disorders of mineral metabolism as a non-traditional risk factor of morbidity and mortality in CKD

14 OBJECTIVES To evaluate the patterns of hyperparathyroidism and biochemical bone mineral disease in chronic kidney disease patients attending renal clinic at the Kenyatta National Hospital

15 Study Design Study Design This study was a descriptive cross-sectional study. Study Area The designated area for the study was Renal Clinic of the Kenyatta National Hospital, Nairobi.

16 Methodology Consecutive sampling of patients at visit to the KNH Renal Clinic between December 2008 and March 2009 SerumBUN, creatinine, albumin, Ca, K, Phos, ALP. - automated clinical chemistry analyzer Cobas Integra 400 Plus (Roche); serum ipth -electro-chemiluminescence immunoassay (ECLIA) on the fully automated immunoanalyzer Elecys

17 PATIENT SELECTION Inclusion Criteria Chronic Kidney Disease with GFR below 90min/1.73m 2. above13 years Signed written informed consent or assent Patients not on dialysis

18 Exclusion criteria Use of glucocorticoids/ vitamin d supplementation/biphosphonates/other drugs that affect bone metabolism. Patients known to have parathyroid disease Patients on dialysis Patients who declined to participate in the study

19 Patient Flow 712 screened 492 excluded 221 eligible 3 Declined consent 218 recruited History,PE & Lab 4 egfr> analyzed

20 CKD Staging

21 Baseline Characteristics No of Patients 214 Male : Female 1.0:1.1 Diabetic(n=78) 36.4% Non-Diabetic (n=136) 63.6% Mean Age yrs 51years Mean SBP mmhg 141 Mean DBP mmhg 88 Mean BWT (Kg) 64.1

22 Laboratory Parameters Parameter Mean in Males Mean in female Overall Mean Serum intact PTH pg/ml(15-65pg/ml) 33.28) Serum Creatinine [60-130µmol/] Mean e GFR ml per min per 1.73 m Serum Phosphorus mmol/l [ µmol] Serum albumin mg/dl(35-50) Corrected Calcium mmol/ [l µmol] Alkaline Phosphotase IU/L [42-141U/L] Haemoglobin level g/dl M-13-15g/dl F-11-13g/dl ) 10.05

23 Distribution of Intact PTH for each stage of CKD Diabetics vs Non-diabetics K/DOQI CKD stage Stage 1>= 90ml/min/1.73m2 Stage ml/min/1.73m2 Stage ml/min/1.73m2 Stage 4(15-29ml/min/1.73m2) Stage 5(< 15ml/min/1.73m2) Frequency Mean serum ipth pg/ml Frequency Mean serum ipth pg/ml NFK- Diabetic Nondiabetic () ) ) ) ) ) Total

24 Distribution of Intact PTH for each stage of CKD Diabetics vs Nondiabetics Parameter Diabetic (%) N=78 Non-diabeti(%) N=136 Total Low Intact PTHN{iPTH<15pg/ml} 45 (46.3) 63(53.7) 108(50.5) Normal Intact PTH {ipth 15-65pg/ml} 20( (65.5) 58(27.1) High Intact PTH {ipth>65pg/ml} 13(27.9) 35(72.1) 48(22.4) Total (100)

25 Patterns of ipth elevation Hyperparathyroid Category Frequency Percentage% Mild Elevation (> % 1.5x65pg/ml) Moderate (1.5x65-2x65pg/ml) % Severe (> 2x65pg/ml) % Total

26 Biochemical Bone turn-over Percentage Prevalence Normal Low High Biochemical bone turnover categories

27 Bone turn-over according to gender. NFK-K/DOQI staging of Chronic Kidney Disease Low turn-over (ipth 65pg/ml, ALP<82.5 IU/L) High turn-over (ipth>97.5pg/ml, ALP>200 IU/l) Male(%) Female(%) Male(%) Female(%) Stage 1( 90ml/min/1.73m2) Stage 2 (60-89ml/min/1.73m2) Stage 3(30-59ml/min/1.73m2) Stage 4(15-29ml/min/1.73m2) Stage 5(< 15ml/min/1.73m2) Total(139) 55(100%) 54(100%) 12(100%) 18(100%)

28 Requirements for K/DOQI CKD stage Serum ipth pg/ml as per K/DOQI guidelines No % Within K/DOQI Guidelines % above K/DOQI guidlines No Total No Stage 3(N=70) Stage 4 (N=42) Stage 5(N=74) Total

29 LIMITATIONS OF THE STUDY The study was performed in a single renal unit, localised at K.N.H (Nairobi) Unable to rule out primary parathyroid disease Postmenopausal women not excluded PTH levels are surrogate marker for bone turnover. Nutritional status and dietary habits of patients not assessed

30 Conclusions SHPT develops and progressively worsens as glomerular function declines. The overall prevalence of SHPT in CKD patients(predialysis)renal clinic at the KNH is lower than it is in American and European poulations.

31 Conclusions Higher prevalence biochemical low turn-over bone disease observed in predialysis patients at KNH than western world. 10.2% of predialyisis population at KNH has SHPT above recommended K/DOQI guidelines and not on management for SHPT

32 Recommendations Serum PTH should be sought early in all patients CKD stages 3 to 5 and appropriate management instituted Studies should be carried out with healthy controls to determine?relative hypoparathyroidism in this population Studies -?Ethnic /nutritional differences??genetic polymorphisims

33 THANK YOU ACKNOWLEDGEMENTS Prof Mc ligeyo Prof Kayima Prof C.F. Otieno Prof Kigondu Dr A.J.O Were