CLINICAL SPECTRUM OF CHRONIC KIDNEY DISEASE: A STUDY OF 50 PATIENTS AT LUMHS

ORIGINAL ARTICLE ISRA MEDICAL JOURNAL | Volume 7 - Issue 4 | Oct - Dec 2015 CLINICAL SPECTRUM OF CHRONIC KIDNEY DISEASE: A STUDY OF 50 PATIENTS AT L...
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ORIGINAL ARTICLE

ISRA MEDICAL JOURNAL | Volume 7 - Issue 4 | Oct - Dec 2015

CLINICAL SPECTRUM OF CHRONIC KIDNEY DISEASE: A STUDY OF 50 PATIENTS AT LUMHS SONIHA ASLAM1, ASLAM GHOURI2, ANIL KUMAR3, SHAHZAMAN KHAN4, YASMEEN IQBAL5 ABSTRACT OBJECTIVE: To evaluate different clinical presentations of chronic kidney disease (CKD) and to raise the index of clinical suspicion so to diagnose and treat CKD at the earliest. STUDY DESIGN: A cross sectional observational study. PLACE AND DURATION: Medical unit III, Liaquat University hospital, Jamshoro from 1st Apr – 30th Sep'2014. METHODOLOGY: We studied fifty patients of CKD, diagnosed by standard clinical criteria. A self administered questionnaire was used to record patient's history and clinical examination. Complete blood count, urine analysis, urea, creatinine, electrolytes, sugar, calcium, spot urine albumin to creatinine ratio and renal ultrasound were done in every patient. In selected cases, renal biopsy was also done. RESULTS: Out of 50 patients, 62% (n = 31) were men, a mean age of 46.22 years (± 12.89 SD), a mean creatinine clearance of 5 mmol/24 hours (±2.16 SD), a mean albumin: creatinine ratio of 49 mg/g (±11.33 SD) and a mean serum creatinine of 16.5 mg/dl (±6.65 SD). Chronic glomerulonephritis (30%), hypertension (24%) and diabetic nephropathy (20%) were the leading causes of CKD. Anemia (94%) was universal finding on laboratory work up. Gastrointestinal manifestations stand out among the clinical presentations with anorexia (76%), nausea (60%) vomiting (40%) and abdominal pain (26%). CONCLUSION: We observed that gastrointestinal disturbances are the commonest clinical presentations in CKD along with anemia, fatigue, dyspnea, hiccups, itching, hypertension and edema. Early diagnosis and management of CKD may prevent or delay the progress to end stage renal disease. KEYWORDS: Chronic kidney disease, Glomerulonephritis, Hypertension, Diabetes, Gastrointestinal manifestations. kidney function5. CKD is generally unrecognized in the early stages, as there are no particular symptoms6. A study done in Karachi observed high prevalence of asymptomatic CKD among the study population7. The problem may be exposed by discovery of anemia, hypertension, or by routine laboratory examination of blood and urine during early stages 2. Patients of CKD may present with indistinguishable symptoms like pallor, fatigue, gastrointestinal disorders like hiccups, nausea and vomiting or with symptoms of heart failure such as dyspnea, orthopnea and edema6. General practitioners easily fail to spot these patients and the delay in diagnosis will affect the patient's treatment and prognosis. If CKD is diagnosed late, such patients have restricted treatment choices like dialysis or transplantation1,6. Complications of CKD consist of increased allcause and cardiovascular mortality, End stage renal disease (ESRD), acute renal injury, cognitive deterioration, anemia, mineral and bone disorders, and fractures4. Early diagnosis and management can prevent or delay the progression of CKD, lessen or evade the development of complications, decrease the risk of cardiovascular disease (CVD) and enhance survival and quality of life6,8. Insensitivity of contemporary screening tools may be the reason for late diagnosis and referrals. Serum urea is an inadequate marker of kidney function, as it fluctuates significantly with hydration and diet8. Serum creatinine is quite insensitive to identify patients with early CKD. The level of serum creatinine can remain normal in spite of the loss of more than 50% of kidney function9. A goldstandard measurement is an isotopic GFR, but not widely available and is expensive 8. A lot of patients with CKD are seen by general practitioners who, though, know the established risk factors for CKD, i.e., diabetes and hypertension but they are less knowledgeable about added risk factors like age and family

INTRODUCTION Chronic kidney disease (CKD) is a global public health concern, with unfavorable outcomes of renal failure, cardiovascular disease (CVD), and early fatality1. The National Kidney Foundation (NKF) and Kidney Disease Outcomes Quality Initiative (K/DOQI) has described CKD as an ailment lasting three or more months with either damage of kidney (ie albuminuria) or reduced kidney function (ie a glomerular filtration rate (GFR) of less than 60 mL/min per 1.73 m2) irrespective of the etiology2. CKD in itself is associated with increasing age, high blood pressure, high blood sugar, high triglycerides, and history of stroke3. Worldwide the occurrence of CKD is anticipated to be 8—16% and the most common cause of chronic kidney disease is diabetes mellitus4. CKD has various clinical presentations depending in part on the extent of reduction of kidney mass and quickness of loss of 1. Assistant Professor of Physical Education and Health Center for Physical Education, Health and Sports Sciences, University of Sindh, Jamshoro 2. Assistant Professor of Medicine 3. Medical Officer Liaquat University of Medical and Health Sciences, Jamshoro 4. Visiting Faculty 5. Professor of Natural Sciences Center for Physical Education, Health and Sports Sciences, University of Sindh, Jamshoro Corresponding to:

Aslam Ghouri Assistant Professor of Medicine 57 Defence Officer's Colony, Hyderabad, Sindh, Pakistan 71000 Email: [email protected]

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radiological investigations. Complete blood count was done for Hb%, TLC, DLC, platelet count and ESR. Urine analysis was performed for albumin, glucose, pus cells, RBCs, casts and crystals. Urea, creatinine, sodium, potassium, chloride, bicarbonate, calcium, phosphorus, uric acid, total proteins, albumin and alkaline phosphatase were done to assess degree of renal involvement. Urine creatinine clearance was calculated by using Cockcroft-Gault equation. Blood sugar was done to detect undiagnosed diabetes or to assess control of diabetes. Spot urine was collected for albumin to creatinine ratio to estimate total 24-hour urinary protein excretion. Ultrasound abdomen was done to assess the size of kidneys. Chest X-ray was requested to detect pleural and pericardial effusions and cardiomegaly. X rays of hands were done to detect subperiosteal erosions. In selected patients, ECG and ECHO were done to look for signs of pericarditis, pericardial effusion, LVH and ischemia. Parathyroid harmone, renal perfusion scans, antinuclear antibodies (ANA), anti double stranded DNA and renal biopsies were done when indicated to confirm the underlying cause. The data was analyzed by SPSS (statistical package for social science) version 18.0. Frequency and percentage were computed for categorical variables like gender, presenting symptoms and signs and etiology of CKD. Mean and standard deviation was computed for quantitative variables like age and laboratory investigations.

history of CKD. Moreover they are unaware of diverse presentations of CKD involving different organ systems of the body resulting in delayed referral of the patients to the nephrologists. Delayed referral is an important predictor of poor outcome10. In a study done at a tertiary care hospital in Pakistan, 48.28% of the consultants and residents were not aware when to refer patients of CKD to nephrologists, based on eGFR11. The number of patients with CKD is increasing in our society because of high prevalence of hypertension, DM and renal stone disease. As CKD can present with variety of symptoms, primary care physicians fail to identify these patients early resulting in delay in diagnosis and treatment. However there is a scarcity of clinical data on CKD in Pakistan, that's why the present study was undertaken to evaluate different clinical presentations of CKD in our population and to facilitate doctors in the periphery to diagnose CKD on clinical grounds where laboratory facilities are lacking. METHODOLOGY This was a cross sectional observational study conducted at medical unit III, Liaquat university hospital, Jamshoro from 1st Apr – 30th Sep'2014. A total of 50 consecutive patients of CKD, admitted in four medical and one nephrology units of the hospital, were included in the study. The inclusion criteria were presence of sign and symptoms of uremia for > 3 months, raised blood urea and creatinine for >3 months and small kidney sizes on ultrasound examination. Patients on dialysis and having co morbidities like malignancy, chronic liver disease, chronic obstructive pulmonary disease and heart failure were excluded. Patients fulfilling the inclusion criteria were enrolled for the study after getting informed consent. Baseline patient's data was collected with the help of a self administered questionnaire which includes patient's history and physical examination. Patients were asked about nausea, vomiting, hiccup, anorexia, abdominal pain, diarrhea, headache, dyspnea, puffy face, leg edema, amount of urine passed in 24 hours, itching, bodyaches, fatigue, loss of libido and amenorrhea. The duration of the symptoms was also recorded. Information about diabetes mellitus, hypertension and renal stones in the past was also noted. Enquiry was also made about family history of renal failure, diabetes and hypertension. Afterwards a detailed physical examination was performed in every patient. The pulse, blood pressure, anemia, edema, JVP, pigmentation, leukonychia, scratch marks, ecchymosis, asterixis, half and half nails were recorded in particular. General survey of other systems was also carried out. Gastrointestinal system was examined for abdominal tenderness and viseromegaly. Cardiovascular system was examined for signs of pericarditis, pericardial effusion and left ventricular hypertrophy. Respiratory system was examined for signs of pleural effusion. CNS was examined for disturbed higher mental functions, involuntary movements and signs of neuropathies. All patients were, then, subjected to various laboratory and

RESULTS The study group included thirty one (62%) males and nineteen (38%) females with male to female ratio of 1.6:1. The age range of patients was 20-70 years with the mean age of 46.22(±12.89 SD). Figure-I show the age distribution of the subjects. The duration of symptoms varied between 3-12 months with the majority of patients having symptoms between 3 - 6 months. The most common presenting symptoms were related to gastrointestinal tract like anorexia (n = 38), nausea (n = 30) and Vomiting (n = 20). Other common presenting symptoms were fatigue (n = 25), dyspnea (n = 15), headache (n = 20), hiccups (n = 18) and itching (n = 8). Table I shows the presenting symptoms of the subjects. Anemia came out to be the universal sign at presentation (n = 47). Hypertension (BP >140/90 mmHg) was present in 12 patients. Majority of hypertensive patients (n = 10) had their blood pressure in stage II according to JNC VII. Table II shows the presenting signs of the subjects. Anemia was the predominant finding on laboratory workup (n = 47) with the mean Hb of 7g/dl (±2.16 SD). Anemia was normocytic in 27 patients, microcytic in 13 patients and macrocytic in 07 patients. The mean blood urea was 245 mg/dl dl (±84.14 SD), the mean serum creatinine was 16.5 mg/dl dl (±6.65 SD) and the mean urinary creatinine clearance was 5 mmol/24 hours (±2.16 SD). Proteinuria and glycosuria was universal on urine analysis with casts in 15 (30%), puss cells in 11 (22%) and RBC in 10 (20%) patients. The mean value of spot urine albumin to creatinine ratio was 49 mg/gm (±11.33 SD). Serum parathyroid harmone assay was performed in 12 patients and it was high only in one patient. Table III shows the laboratory investigations of the

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subjects. Ultrasound abdomen was performed in all patients and it shows decreased size of the kidneys in 30 patients (60%). Table IV shows the radiological findings in the subjects. Regarding etiology of CKD, Glomerulonephritis was the most common cause (n = 15 30%) followed by hypertension (n = 12

24%) and diabetic nephropathy (n = 10 20%). Other etiologies were renal stone disease (n = 4 8%) and polycystic kidney disease (n = 1 2%). The etiology of CKD remains unknown in 16% (n= 8) cases.

TABLE-I: FREQUENCY OF SYMPTOMS IN THE SUBJECTS (n=50) FREQUENCY

PERCENTAGE

Anorexia

38

76

Nausea

30

60

Bodyaches/Fatigue

25

50

Vomiting

20

40

Abdominal Pain

20

40

Headache

20

40

Hiccups

18

36

Dyspnea

15

30

Diarrhea

10

20

Itching

08

16

Unconsciousness

03

06

Fits

02

04

Restless leg

02

04

Parasthesia/numbness

01

02

Tremors

01

02

SYMPTOM

Age in years FIGURE - 1: AGE DISTRIBUTION OF THE SUBJECTS (n = 50)

TABLE-III: LABORATORY FINDINGS OF THE SUBJECTS (n = 50) SIGNS

TABLE - II: FREQUENCY OF SIGNS IN THE SUBJECTS (n = 50)

MEAN RANGE

STANDARD DEVIATION

Raised blood Urea (mg/dl)

245

100-390

84.14

Raised serum

16.5

6-27

6.65

5.0

2-8

2.16

49

39-89

11.33

Creatinine (mg/dl)

FREQUENCY

PERCENTAGE

Pallor

47

94

clearance (mmol/24 hr)

Edema

15

30

High Spot urine albumin

Hypertension

12

24

to creatinine ratio(mg/g)

LVH

12

24

Reduced hemoglobin (g/dl)

7.0

4-10

2.16

Raised JVP

12

24

FBS (mg/dl)

120

90-150

17.75

Hepatomegaly

12

24

RBS (mg/dl)

230

160-300

40.84

Pleural Effusion

05

10

Raised serum

146

144-148

1.58

Leukonychia

05

10

sodium (mmol/l)

Ascites

04

8

Raised serum

5.5

5.1-6.1

0.70

Dry skin

04

8

potassium (mmol/l)

Pulmonary Edema

04

8

Low serum calcium (mg/dl)

6.0

5-8

1.41

6.8

4.5-8

1.52

SIGNS

Decreased creatinine

Pigmentation

03

6

High serum

Half and half nails

03

6

phosphate (mg/dl)

Bone Tenderness

02

4

Alkaline phosphatase (µ/l)

180

60-300

69.71

Pericardial Effusion

01

2

Raised uric Acid (mg/dl)

9.5

9-10

0.70

Pericardial Rub

01

2

24 hour Urine for

3.0

1-5

1.58

Neuropathy

01

2

Protein (g/24 hours)

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TABLE-IV: RADIOLOGICAL FINDINGS OF THE SUBJECTS (n=50) FREQUENCY

PERCENTAGE

1. Cardiomegaly

12

24

2. Pleural Effusion

05

10

3. Pericardial Effusion

04

08

30

60

01

02

TEST CXR

Ultrasound Abdomen  Reduced size of kidneys X Ray of Hands  Subperiosteal Erosions TABLE-V: COMPARISON OF ETIOLOGY OF CKD WITH OTHER STUDIES. ETIOLOGY (%)

PRESENT STUDY

PARKASH et al22

JAMRO et al13

GENERAL HOSPITAL LAHORE15

KIDNEY CENTER KARACHI16

15.4

Chronic Glomerulonephritis

30

7

26.7

44.3

Hypertension

24

18

23.3

8.8

Diabetes Mellitus

20

46

16.9

13.9

Obstructive Uropathy

8

13

14

16.2

10.1

Polycystic kidney disease

2

01

-

2.9

6.3

Reflux Nephropathy

-

-

24.5

-

-

Chronic interstitial nephritis

-

14

-

-

-

DISCUSSION

done on old patients above 60 years who might be suffering from prostatic hyperplasia. A study performed on children demonstrated that reflux nephropathy is a common cause of CKD13. While we didn't found a single patient of reflux nephropathy, this may be due to the fact that our patients were more than 20 years of age. The incidence of cystic kidney disease in our study was low. Similar results were found in other studies13,23. Table V compares the etiology of CKD with other studies. Many of the earlier analyses in CKD patients have recognized wide-ranging presentations. Present study also authenticates the presence of variable clinical characteristic s in patients with CKD as most of the patients showed involvement of different organ systems. The symptoms pertaining to gastrointestinal tract were highly common at presentation such as anorexia, nausea and vomiting. This is in similar with the studies done at Mayo hospital Lahore14 and kidney center Karachi16 which showed that nausea and vomiting were the predominant clinical features. Similarly cardiovascular symptoms e.g. dyspnea, edema and hypertension were also predominant in current study. Our outcome match with the studies performed in Nigeria22 and China24, which revealed that hypertension was the main cardiovascular finding. Left ventricular hypertrophy was quiet frequent in our patients and this go with a study performed in France25. We found only two patients each of pericarditis and pericardial effusion. This is contrary to the research done in China24 which observed pericarditis and pericardial effusion in bulk of patients. In our study, the frequency of cases with neurological signs like parasthesia, numbness and tremors were less. This is in accordance with the facts observed in a study done in China24. Seizures were

Chronic kidney disease (CKD) is a common progressive ailment which ultimately results in end stage renal disease (ESRD). Renal replacement therapy is the only treatment option for these patients which is costly and not frequently available in our setup12,13. Often, CKD is difficult to recognize in early stages because of its subtle and broad range of presentations resulting in late referrals and restricted treatment options. Timely intervention may arrest or delays the disease progression and need for renal replacement therapy. Present study observed that CKD is more common in males and happen most frequently in 5th and 6th decades. This is in accordance with the studies done in India14, Lahore15, Karachi16, USA17 and China18. The most common causes of CKD in our study were Glomerulonephritis, hypertension and Diabetes mellitus. A study done in China18 and two local studies, done in Lahore15 and Karachi16 observed matching outcome. Glomerulonephritis was also the major cause of CKD in studies done in various parts of the world13,14,19,20,21. However a study performed on elderly CKD patients in eastern India shows a less prevalence of glomerulonephritis22. In our study, hypertension was among the primary causes of CKD; the study done in India also shows similar results23. In our research, diabetes mellitus was one of the leading causes of CKD. This is in accord with other studies14, 19,23 . The incidence of obstructive uropathy was low in present study and all four patients had renal stone disease. This is not consistent with study done on children which tells that renal stone disease is quite frequent cause of CKD13. Two studies done in India also observed obstructive uropathy as a main cause of CKD22,23. This may possibly be because the studies in India were

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exceptional in our patients. This is in disagreement with a research done on children at Mayo hospital Lahore12 which found that seizures are not uncommon in CKD patients. Pulmonary edema was an uncommon finding in present study. This is in disparity with the study done in Karachi16 that shows high percentage of pulmonary edema. In our study anemia was the universal finding as the study of Leishili24 and Jamro13 observed. Edema was a familiar finding in our patients which is in accordance with the verdicts of other studies12, 20. But in a study by Leishili24, edema was present in only 7% patients.

379(9811):165-80. 9. Levin A. Consequences of late referral on patient outcomes. Nephrol Dial Transplant. 2000; 15 Suppl 3:8-13. 10. Yaqub S, Kashif W, Raza M Q, Aaqil H, Shahab A, Chaudhary M A, Hussain S A. General practitioners' knowledge and approach to chronic kidney disease in Karachi, Pakistan. Indian J Nephrol. 2013; 23(3): 184–90. 11. Tamizuddin S, Ahmed W. Knowledge, attitude and practices regarding chronic kidney disease and estimated GFR in a tertiary care hospital in Pakistan. J Pak Med Assoc 2010; 60(5): 342. 12. Khan I W, Irfan K, Ahmad T M, Khan H I. Spectrum of clinical presentation of Chronic Renal Failure in children. Pak Paed J. 2002; 26(4):167-71. 13. Jamro S, Channa N A, Shaikh A H, Ramzan A. Chronic Renal Failure in Children. J Pak Med Assoc 2003; 53(4):140-42 14. Agarwal S K, Dash S C. Spectrum of renal diseases in Indian adults. J Assoc Physicians India. 2000; 48(6):594-600. 15. Iqbal S, Javed S H, Khan J H. Pattern of renal failure disease at Lahore General Hospital Lahore. PGMJ 1993; (2):107-16. 16. Kumar H, Alam F, Naqvi S A J. Experience of Hemodialysis at Kidney Center. J Pak Med Assoc. 1992; 42(10):234-36. 17. Chevalier R L. Estimating work force and training requirements for Nephrologists through the year 2010. Pediatric perspective journal of American society of Nephrology. 1997; 8:846. 18. Cohen J J, Harrgtion J T, Madias N E. End stage Renal Disease in China. Kidney Int. 1996; 49:287-300. 19. Aggarwal H K, Yashodara B M, Nand N, Sonia, Chakrabarti D, Bharti K. Spectrum of renal disorders in a tertiary care hospital in Haryana. J Assoc Physicians India. 2007; 55:198202. 20. Odetunde O I, Okafor H U, Uwaezuoke S N, Ezeonwu B U, Adiele K D, Ukoha O M. Chronic kidney disease in children as seen in a tertiary hospital in Enugu, South-East, Nigeria. Niger J Clin Pract. 2014; 17(2):196-200. 21. Al Wakeel J S, Mitwalli A H, Tarif N, Alam A A, Hammad D, Abu-Aisha H et al. Spectrum and outcome of primary glomerulonephritis. Saudi J Kidney Dis Transpl. 2004; 15(4):440-46. 22. Parkash J, Hota J K, Singh S, Sharma O P. Clinical Spectrum of Chronic Renal Failure in the Elderly: a Hospital Based Study from Eastern India. Int Urol Nephrol 2006; 38: 821-27. 23. Prakash J, Saxena R K, Sharma O P, Usha. Spectrum of renal diseases in the elderly: single center experience from a developing country. Int Urol Nephrol. 2001; 33(2):227-33 24. Li L, et al. End Stage renal disease in China: Kidney Int. 1996; 49(1): 287-301 25. London G M, Guerin A P, Marchais S J, Pannier B, Safar M E, Day M, et al: Cardiac and arterial interaction in end stage renal disease. Kidney Int. 1996; 50(2):600-8.

CONCLUSION We conclude that glomerulonephritis, hypertension and diabetes mellitus are the most common causes of CKD. The commonest clinical presentations are anemia, fatigue, anorexia, nausea, vomiting, dyspnea, hiccups, itching, hypertension and edema. As CKD has diverse clinical manifestations involving any organ system of the body, more and more studies are needed to recognize the various presentations of this disease in the local population. Early diagnosis and management of these conditions may prevent or delay the progress to end stage renal disease. REFERENCES 1. Levey A S, Eckardt K U, Tsukamoto Y, Levin A, Crosh J, Rossert J et al. Chronic kidney disease: De?nition and classi?cation. Kidney Int. 2005; 67(6):2089–100. 2. National kidney foundation: K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classi?cation and Strati?cation. Am J Kidney Dis 2002; 39 (Suppl 1):S1–S266, 2002. 3. Jessani S, Bux R, Jafar T H. Prevalence, determinants, and management of chronic kidney disease in Karachi, Pakistan -a community based cross-sectional study. BMC Nephrology 2014; 15:90. 4. Jha V A, Garcia-Garcia G, Iseki K, Li Z, Naicker S , Plattner B, et al. Chronic kidney disease: global dimension and perspectives. The Lancet. 2013 20;382(9888):260-72 5. Bargman J M, Skorecki K. Chronic kidney disease. In: Fauci S A, Kasper D L, Long D L, Braunwald E, Hauser S L, Jameson J L et al, eds. Harrison's Principle of Internal Medicine 17th Ed: New York Mc Graw Hill; 2008: 1761-72 6. Chronic kidney disease: early identification and management of chronic kidney disease in adults in primary and secondary care; NICE Clinical Guidelines (July 2014) 7. Imran S, Sheikh A, Saeed Z I, Khan S A, Malik A O, Patel J, et al. Burden of chronic kidney disease in an urban city of Pakistan, a cross-sectional study. J Pak Med Assoc. 2015; 65(4): 366. 8. Levey AS, Coresh J. Chronic kidney disease. Lancet. 2012 14;

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