Original research paper
Renal function in adult Jamaicans with homozygous sickle cell disease Monika R. Asnani, Marvin E. Reid
dP roo f
Sickle Cell Unit, Tropical Medicine Research Institute, University of the West Indies, Jamaica, WI, USA
cte
Objectives: As populations with sickle cell disease (SCD) live longer, it is likely that the burden of renal dysfunction will be an increasing challenge for patients. In this study, we aim to determine the prevalence of renal dysfunction and its possible predictors in persons with SCD. Methods: Ninety-eight patients with the homozygous SCD (SS disease;55 females, 43 males; mean age 34 ± 2.3 years) in their steady state had measurements of glomerular filtration rate (GFR) using 99mTc-DTPA nuclear renal scan, serum creatinine, and urinary albumin: creatinine ratio. Other haematological and biochemical measurements and data on clinical events were completed for each individual. Results: Chronic kidney disease (CKD) stages 3 and above was present in 6% of the study population, and 65.3% had albuminuria. Hyperfiltration occurred in 24.5% patients with two-thirds having albuminuria as well. Serum creatinine was an insensitive marker of renal dysfunction as started rising after measured GFR fell below 50 mls/min/1.73 m2. Multiple regression modelling showed serum creatinine and height to be significantly associated with GFR. Serum creatinine was also significantly associated with albuminuria, and age was not a predictor in any of the models. There was no association with markers of haemolysis. Conclusion: We conclude that the burden of renal dysfunction is quite high in this young cohort with SS disease. Serum creatinine is a late and insensitive marker of worsening glomerular function, and screening for albuminuria could begin early in life. Longitudinal studies will continue to increase our understanding of pathophysiological mechanisms that lead to CKD in this specific population. Keywords: Glomerular filtration rate, SS disease, Hyperfiltration, Albuminuria, Chronic kidney disease
Introduction
Un
co
rre
Chronic kidney disease (CKD) comprises a continuum of renal function and is usually determined based on the presence of a marker of structural damage to the kidney (e.g. presence of significant amounts of protein such as albumin in the urine) or a decreased estimated glomerular filtration rate (GFR) over 3 months or more.1,2 There is huge economic and social cost associated with CKD, especially with endstage renal disease,3,4 and CKD has been in fact declared as a public health problem. Within the Caribbean as well, CKD is on a rapid incline as the burden of non-communicable, lifestyle diseases increases. However, resources for managing CKD, especially renal replacement therapy, are limited in most, if not all, Caribbean countries.5 It is an imperative, therefore, to screen and diagnose CKD early in its course so that potentially therapeutic interventions can be applied and therefore prevent complications
Correspondence to: Monika R. Asnani, Sickle Cell Unit, Tropical Medicine Research Institute, University of the West Indies, Mona Campus, Kingston 7, Jamaica, WI, USA. Email: [email protected]
© W. S. Maney & Son Ltd 2014 DOI 10.1179/1607845414Y.0000000213
of CKD such as kidney failure and worsening cardiovascular diseases.6 Sickle nephropathy is a well-known complication of sickle cell disease (SCD) and manifestations can begin even in early childhood. Various manifestations include hyposthenuria resulting in enuresis, haematuria, and renal papillary necrosis, nephrotic syndrome, urinary tract infections including pyelonephritis, tubular abnormalities, albuminuria, and end-stage renal failure. Although in the past, emphasis during managing persons with SCD was placed more on severe, acute, and life-threatening complications of the disease, end-stage organ failure in these persons is now coming to the forefront as contributing to the morbidity and mortality in SCD7 as populations live longer.8 Even then, focus on renal complications has been scattered despite the fact that as far as three decades ago renal failure was found to account for ∼18% of deaths over the age of 20 years in persons with SCD.9 A more recent study by Serjeant et al. 10 has demonstrated that up to 85% of elderly SS persons (i.e. over the age of 60 years) have renal impairment in their Jamaican clinic population,
Hematology
2014
VOL.
0
NO.
0
1
Renal function in SS disease
and that in fact impaired renal function was the main clinical complication in these elderly survivors.11 Barton et al. 12 have earlier described SCD to rank at 11th position as a cause of chronic renal failure in Jamaica and contributing to 0.7% of the cases. In the present study, we propose to determine the prevalence of renal dysfunction (as estimated by albumin excretion in the urine and GFR measurements) and CKD in persons with homozygous SCD (SS disease). We also aim to determine possible predictors and associated factors for GFR and albumin excretion in this population.
Methods and materials
cte
This cross-sectional study was conducted in persons with the homozygous SS disease from the Jamaica Sickle Cell Cohort Study (JSCCS) from July 2011 to April 2012. The cohort has been followed at the Sickle Cell Unit (SCU) at University of the West Indies in Jamaica since birth and participants were between the ages of 29 and 39 years during the study period. Ninety-eight participants were available and recruited to the study when they had nil acute illnesses, nil blood transfusion in the preceding 1 month, and in the non-pregnant state. None of the patients were on hydroxyurea or a chronic blood transfusion programme. The study was granted ethical approval by the University of the West Indies/University Hospital of the West Indies Ethical Committee. The study was designed and performed in adherence with the Declaration of Helsinki. Written, informed consent was obtained from all participants involved in the study.
measurements. Haematological measurements included haemoglobin (Hb), white blood cell, platelets, and reticulocyte counts and were performed at the SCU laboratory itself. Serum creatinine and lactate dehydrogenase (LDH), as well as urine ACR were tested using the VITROS® 350 Analyser at a private laboratory in Kingston, Jamaica. Serum and urinary creatinine were measured using the VITROS CREA slide method which uses a multi-layered, analytical element coated on a polyester support. This employs an enzymatic method of determining creatinine levels in the ranges of 4–1238 μmol/l (0.05–14 mg/dl) in serum and 106–30631 μmol/l (1.2–346.5 mg/dl) in urine samples. The values assigned to the VITROS Chemistry Products Calibrator Kit for creatinine are traceable to a gas chromatography isotope dilution mass spectrometry method13 and National Institute of Standards and Technology SRM® 914 creatinine standard reference material. Bilirubin levels up to 342 μmol/l (20 mg/ dl) were shown to have nil interference, i.e. F
Predictors
Measured GFR, mls/min/1.73 m2
0.37
Renal function in adult Jamaicans with homozygous sickle cell disease Monika R. Asnani, Marvin E. Reid
dP roo f
Sickle Cell Unit, Tropical Medicine Research Institute, University of the West Indies, Jamaica, WI, USA
cte
Objectives: As populations with sickle cell disease (SCD) live longer, it is likely that the burden of renal dysfunction will be an increasing challenge for patients. In this study, we aim to determine the prevalence of renal dysfunction and its possible predictors in persons with SCD. Methods: Ninety-eight patients with the homozygous SCD (SS disease;55 females, 43 males; mean age 34 ± 2.3 years) in their steady state had measurements of glomerular filtration rate (GFR) using 99mTc-DTPA nuclear renal scan, serum creatinine, and urinary albumin: creatinine ratio. Other haematological and biochemical measurements and data on clinical events were completed for each individual. Results: Chronic kidney disease (CKD) stages 3 and above was present in 6% of the study population, and 65.3% had albuminuria. Hyperfiltration occurred in 24.5% patients with two-thirds having albuminuria as well. Serum creatinine was an insensitive marker of renal dysfunction as started rising after measured GFR fell below 50 mls/min/1.73 m2. Multiple regression modelling showed serum creatinine and height to be significantly associated with GFR. Serum creatinine was also significantly associated with albuminuria, and age was not a predictor in any of the models. There was no association with markers of haemolysis. Conclusion: We conclude that the burden of renal dysfunction is quite high in this young cohort with SS disease. Serum creatinine is a late and insensitive marker of worsening glomerular function, and screening for albuminuria could begin early in life. Longitudinal studies will continue to increase our understanding of pathophysiological mechanisms that lead to CKD in this specific population. Keywords: Glomerular filtration rate, SS disease, Hyperfiltration, Albuminuria, Chronic kidney disease
Introduction
Un
co
rre
Chronic kidney disease (CKD) comprises a continuum of renal function and is usually determined based on the presence of a marker of structural damage to the kidney (e.g. presence of significant amounts of protein such as albumin in the urine) or a decreased estimated glomerular filtration rate (GFR) over 3 months or more.1,2 There is huge economic and social cost associated with CKD, especially with endstage renal disease,3,4 and CKD has been in fact declared as a public health problem. Within the Caribbean as well, CKD is on a rapid incline as the burden of non-communicable, lifestyle diseases increases. However, resources for managing CKD, especially renal replacement therapy, are limited in most, if not all, Caribbean countries.5 It is an imperative, therefore, to screen and diagnose CKD early in its course so that potentially therapeutic interventions can be applied and therefore prevent complications
Correspondence to: Monika R. Asnani, Sickle Cell Unit, Tropical Medicine Research Institute, University of the West Indies, Mona Campus, Kingston 7, Jamaica, WI, USA. Email: [email protected]
© W. S. Maney & Son Ltd 2014 DOI 10.1179/1607845414Y.0000000213
of CKD such as kidney failure and worsening cardiovascular diseases.6 Sickle nephropathy is a well-known complication of sickle cell disease (SCD) and manifestations can begin even in early childhood. Various manifestations include hyposthenuria resulting in enuresis, haematuria, and renal papillary necrosis, nephrotic syndrome, urinary tract infections including pyelonephritis, tubular abnormalities, albuminuria, and end-stage renal failure. Although in the past, emphasis during managing persons with SCD was placed more on severe, acute, and life-threatening complications of the disease, end-stage organ failure in these persons is now coming to the forefront as contributing to the morbidity and mortality in SCD7 as populations live longer.8 Even then, focus on renal complications has been scattered despite the fact that as far as three decades ago renal failure was found to account for ∼18% of deaths over the age of 20 years in persons with SCD.9 A more recent study by Serjeant et al. 10 has demonstrated that up to 85% of elderly SS persons (i.e. over the age of 60 years) have renal impairment in their Jamaican clinic population,
Hematology
2014
VOL.
0
NO.
0
1
Renal function in SS disease
and that in fact impaired renal function was the main clinical complication in these elderly survivors.11 Barton et al. 12 have earlier described SCD to rank at 11th position as a cause of chronic renal failure in Jamaica and contributing to 0.7% of the cases. In the present study, we propose to determine the prevalence of renal dysfunction (as estimated by albumin excretion in the urine and GFR measurements) and CKD in persons with homozygous SCD (SS disease). We also aim to determine possible predictors and associated factors for GFR and albumin excretion in this population.
Methods and materials
cte
This cross-sectional study was conducted in persons with the homozygous SS disease from the Jamaica Sickle Cell Cohort Study (JSCCS) from July 2011 to April 2012. The cohort has been followed at the Sickle Cell Unit (SCU) at University of the West Indies in Jamaica since birth and participants were between the ages of 29 and 39 years during the study period. Ninety-eight participants were available and recruited to the study when they had nil acute illnesses, nil blood transfusion in the preceding 1 month, and in the non-pregnant state. None of the patients were on hydroxyurea or a chronic blood transfusion programme. The study was granted ethical approval by the University of the West Indies/University Hospital of the West Indies Ethical Committee. The study was designed and performed in adherence with the Declaration of Helsinki. Written, informed consent was obtained from all participants involved in the study.
measurements. Haematological measurements included haemoglobin (Hb), white blood cell, platelets, and reticulocyte counts and were performed at the SCU laboratory itself. Serum creatinine and lactate dehydrogenase (LDH), as well as urine ACR were tested using the VITROS® 350 Analyser at a private laboratory in Kingston, Jamaica. Serum and urinary creatinine were measured using the VITROS CREA slide method which uses a multi-layered, analytical element coated on a polyester support. This employs an enzymatic method of determining creatinine levels in the ranges of 4–1238 μmol/l (0.05–14 mg/dl) in serum and 106–30631 μmol/l (1.2–346.5 mg/dl) in urine samples. The values assigned to the VITROS Chemistry Products Calibrator Kit for creatinine are traceable to a gas chromatography isotope dilution mass spectrometry method13 and National Institute of Standards and Technology SRM® 914 creatinine standard reference material. Bilirubin levels up to 342 μmol/l (20 mg/ dl) were shown to have nil interference, i.e. F
Predictors
Measured GFR, mls/min/1.73 m2
0.37
