|Year : 2022 | Volume
| Issue : 4 | Page : 267-274
Assessment of level of care of diabetic patients with nephropathy in predialysis stage 4 in Tanta
Ahmed A A Elmoghany1, Mohammed H El-Naggar1, Ali El-Sherbiny2, Ingy A W Ibrahim1
1 Department of Internal Medicine, Tanta University, Tanta, Egypt
2 Department of Public Health and Community Medicine, Faculty of Medicine, Tanta University, Tanta, Egypt
|Date of Submission||31-Dec-2019|
|Date of Acceptance||13-Jul-2021|
|Date of Web Publication||22-May-2023|
Ahmed A A Elmoghany
Department of Internal Medicine, Faculty of Medicine, Tanta University, Elftooh School Street, In front of Health Insurance Hospital, El-Santa City, El-Gharbya 31511
Source of Support: None, Conflict of Interest: None
Background Stage 4 chronic kidney disease (CKD) in comparison with earlier stages of CKD is associated with higher morbidity, mortality, and costs, and current guidelines recommend greater intensity of care for patients with stage 4 disease. Aim Our study assessed the level of care of patients with diabetic nephropathy (DN) in predialysis stage (CKD stage 4) in Tanta. Patients and methods A total of 257 patients experiencing DN stage 4 from Tanta were subjected to a questionnaire sheet that included age; duration of diabetes; time of diagnosis of DN; treatment of hypertension; patient diet; antidiabetic drugs; level of serum creatinine; estimated glomerular filtration rate; hemoglobin level; serum levels of Ca, Ph, parathyroid hormone, Na, K, and HCO3; lipid profile; statin therapy; and hemoglobin A1c. The data collected were compared with Kidney Disease: Improving Global Outcomes clinical practice guideline for the evaluation and management of CKD. Results Of the 257 patients, 27.6% were type 1 diabetics and 72.4% were type 2. The mean duration of diabetes was 12.43 years (±6.388). Overall, 29.9% had uncontrolled elevated blood pressure, of whom 27.2% were on no antihypertensive drugs. Renin-angiotensin-aldosterone system blockage agents were used in 52.1% of patients. Overall, 57.2% had good control of diabetes. Dyslipidemia was found in 49.4% patients of them 62.2% patients were on no statin therapy. Hypocalcemia was found in 5.4% patients, hyperphosphatemia was found in 12.4% patients, 4.7% had secondary hyperparathyroidism, 79.8% had bicarbonate level below normal range, 9.7% had mild elevate potassium level, and 20.4% had anemia. Conclusion Our patients reached stage 4 early after few years of diabetes, and parameters that need more level of care include hypertension, diabetes, treatment used for diabetes, dyslipidemia, and acidosis.
Keywords: chronic kidney disease stage 4, diabetic nephropathy care, predialysis stage
|How to cite this article:|
Elmoghany AA, El-Naggar MH, El-Sherbiny A, Ibrahim IA. Assessment of level of care of diabetic patients with nephropathy in predialysis stage 4 in Tanta. Tanta Med J 2022;50:267-74
|How to cite this URL:|
Elmoghany AA, El-Naggar MH, El-Sherbiny A, Ibrahim IA. Assessment of level of care of diabetic patients with nephropathy in predialysis stage 4 in Tanta. Tanta Med J [serial online] 2022 [cited 2023 May 31];50:267-74. Available from: http://www.tdj.eg.net/text.asp?2022/50/4/267/377252
| Introduction|| |
International Diabetes Federation has stated that diabetes mellitus (DM) is a major health problem worldwide . According to statistics of International Diabetes Federation, two individuals develop diabetes every 10 s worldwide, and two individuals die of diabetes-related conditions every 10 s worldwide.
DM is the most frequent cause of chronic renal failure in both developed and developing countries . Careful monitoring of diabetic patients with chronic kidney disease (CKD) and timely planned initiation of renal replacement therapy are of outmost importance, as delayed initiation of dialysis is associated with excess mortality, morbidity, and cost .
According to the National Kidney Foundation (NKF), CKD is classified into five stages according to estimated glomerular filtration rate (eGFR): stage 1 with normal or relatively high GFR (≥90 ml/min/1.73 m2), stage 2 with mild reduction in GFR (60–89 ml/min/1.73 m2), stage 3 with moderate reduction in GFR (30–59 ml/min/1.73 m2), stage 4 with severe reduction in GFR (15–29 ml/min/1.73 m2), and stage 5 with established kidney failure (GFR<15 ml/min/1.73 m2) .
The commonest method used for calculating eGFR depends on the Modification of Diet in Renal Disease equation, which uses four variables, including creatinine, age, sex, and race, to calculate the eGFR .
Stage 4 CKD in comparison with earlier stages of CKD is associated with higher morbidity, mortality, and costs, and the current guidelines recommend greater intensity of care for patients with stage 4 disease .
Early detection of diabetic nephropathy (DN), adoption of multifactorial interventions targeting the main risk factors (hyperglycemia, hypertension, dyslipidemia, and smoking), and use of agents with renoprotective effect, such as renin-angiotensin-aldosterone system (RAAS) blockage, do indeed reduce the progression of renal disease and cardiovascular mortality .
The Standards of Medical Care in Diabetes 2017 of the American Diabetes Association (ADA) , the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 guidelines , and the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines for the management of diabetes with CKD  recommend a target hemoglobin A1c (HbA1c) of less than or equal to 7.0% to prevent or retard the progression of CKD.
The United Kingdom Prospective Diabetes Study (UKPDS) provided strong evidence that blood pressure (BP) control can reduce the development of diabetic kidney disease (DKD) . Renin-angiotensin system inhibition has been demonstrated to delay the onset of elevated albuminuria .
The effect of lipid reduction on progression of DN is still unknown. However, there is evidence that lipid reduction by statin agents might preserve eGFR and decrease proteinuria in diabetic patients .
In CKD stage 4, metabolic complications are prevalent and clinically present. Severe anemia may contribute to left ventricular failure, cerebrovascular accidents, and lower quality of life. Recent studies have consistently shown that aiming for normal hemoglobin levels may have detrimental effects; therefore, hemoglobin targets are set at the narrow range of 10.0–12.0 g/dl .
The parathyroid glands grow in response to persistent hypocalcemia, hyperphosphatemia, and vitamin D deficiency . Early vitamin D substitution by cholecalciferol and phosphate control is important to prevent hyperparathyroidism .
In this study, we aimed to assess the level of care of patients with DN in predialysis stage (CKD stage 4) in Tanta.
| Patients and methods|| |
This is a prospective cross-sectional study that included 257 patients having DN stage 4, comprising 125 patients from Tanta University Hospital, 59 patients from Medical Insurance Hospital (Elmogamaa Elteby), and 73 patients from Elmenshawy Hospital. The duration of this study was 6 months, starting from the November 2017 to April 2018. The ethics committee of our institution approved this study; informed consent was obtained from all patients after full explanation of the procedure. It was approved by the Research Ethical Committee, Faculty of Medicine, Tanta University, with approval number 31838/10/17.
A simple random sample was selected through a computer-based list.
- (1) The sample size was calculated using Minitab statistical program ver.17. The minimal sample size for a single proportion was calculated, and it was 233 patients with DN stage 4 putting in consideration that the hypothesis probability was 30% (for bad outcome) and alternative probability was 40 and at 90% power of the test.
- (2) The cases were increased by 24 cases (about 10%) to compensate for the cases unwilling to participate. Therefore, the sample size was 257 patients with DN stage 4.
Patients with DN stage 4 treated in Tanta University Hospital, Medical Insurance Hospital (Elmogamaa Elteby), and Elmenshawy Hospital outpatient clinics have been included in the study after taking consent from them to use their data for the research purposes and use them confidentially.
The following were the exclusion criteria:
- (1) Patients with other causes of renal disease.
- (2) Patients on dialysis.
- (3) Patients with other overlapping metabolic disorders.
Clinical and laboratory assessments
- (1) The target group was subjected to a predesign questionnaire sheet, which included the following:
- (a) Data of patients, which was collected from the targeted patients and their files.
- (b) Data included age, sex, duration of diabetes, time of diagnosis of DN, treatment of hypertension, patient diet, self-monitoring of blood glucose, and antidiabetic drugs used for treatment.
- (c) Investigations, which included level of serum creatinine, eGFR, hemoglobin level, and serum levels of Ca, Ph, parathyroid hormone (PTH), Na, K, and HCO3.
- (d) Moreover, it included lipid profile, statin therapy, and HbA1c, with own patient target for HbA1c.
- (2) eGFR was determined according to abbreviated Modification of Diet in Renal Disease equation.
GFR (ml/min/1.73 m2)=186×(Scr)-1.154×(Age)-0.203× (0.742 if female)×(1.212 if African American) .
- (3) Data collected were compared with KDIGO clinical practice guideline for the Evaluation and Management of CKD.
The collected data were organized, tabulated, and statistically analyzed using SPSS software (Statistical Package for the Social Sciences, version 16; SPSS Inc., Chicago, Illinois, USA).
For quantitative data, the mean and SD were calculated.
The categorical variables were statistically analyzed by the χ2 test.
For qualitative data, comparison between two groups or more was done using t test and analysis of variance test.
For predictors of outcome of any parameter, stepwise regression analysis was used.
| Results|| |
Of the 257 patients, 136 (52.9%) were males and 121 (47.1%) were females. A total of 71 (27.6%) had type 1 diabetes and 186 (72.4%) had type 2. The mean age was 51.26 years (±14.259). The mean duration of diabetes was 12.43 years (±6.388), and the mean of time of diagnosis of DN was 29.03 months (±19.554).
Of the 257 patients, 77 (29.9%) had uncontrolled elevated BP, and 21 (27.2%) were on no antihypertensive drugs.
Usage of renin-angiotensin-aldosterone system blockage agents
A total of 134 (52.1%) patients used RAAS blockage drugs as antihypertensive drug.
Control of diabetes
Assessment of diabetic control with HbA1c revealed that of 257 patients, 147 (57.2%) had good control (HbA1c≤7%), 62 (24.1%) had fair control (HbA1c=7.1–7.9%), whereas 41 (16%) and seven (2.7%) patients had high (HbA1c=8–10%) and extremely high (HbA1c >10%), respectively.
Of 147 good controlled patients, 102 (69.3%) used insulin alone, 10 (6.8%) used insulin with metformin, and 35 (23.8%) used oral hypoglycemic drugs.
Regimens that have good control of HbA1c were insulin with metformin, insulin, and metformin, with percentages of 71.4, 60.4, and 60%, respectively.
Bone mineral disease parameters
Hypocalcemia was found in 14 (5.4%) patients, elevated phosphate was found in 32 (12.4%) patients, whereas 12 (4.7%) patients had secondary hyperparathyroidism.
Dyslipidemia was found in 127 (49.4%) patients, and of them, 79 (62.2%) patients were without statin therapy.
Acidosis and hyperkalemia
Metabolic acidosis was assessed with bicarbonate level and showed that of 257 patients, 205 (79.8%) patients had bicarbonate level below normal rang and 25 (9.7%) patients had mild elevated potassium level.
Anemia was assessed with hemoglobin and transferrin saturation and revealed that 55 (20.4%) patients had anemia, and of them, 47 (85.4%) had iron-deficiency anemia.
[Table 1] shows the predictors of the outcome of diabetes as measured by HbA1c. It revealed that unhealthy diet, high PO4 level, low T sat level, low hemoglobin level, type 2 DM, and usage of oral hypoglycemic drugs for DM were considered as predictor factors for high level of HbA1c with the effect of 20.4%.
|Table 1: The predictors of outcome of diabetes as measured by HbA1c (stepwise regression analysis)|
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[Table 2] shows the predictors of the outcome of DN stage 4 as measured by eGFR. It revealed that male sex, high creatinine level, old age, high PTH level, high diastolic BP, and presence of iron-deficiency anemia were considered as predictive factors for high level of eGFR.
|Table 2: The predictors of outcome of diabetic nephropathy stage 4 as measured by estimated glomerular filtration rate (stepwise regression analysis)|
Click here to view
[Table 3] shows the correlation between level of eGFR on one side and some of the study variables on the other side. It revealed that female sex, type 2 DM, control of systolic and diastolic BP, and normal hemoglobin level are positively correlated with high level of eGFR in the study group.
|Table 3: Correlation between level of estimated glomerular filtration rate and the studied variables|
Click here to view
[Table 4] shows the relationship between level of control of HbA1c and treatment used for diabetes in the study group. It revealed that insulin with metformin, insulin alone, and metformin alone have good control of HbA1c level, with percentages of 71.4, 60.4, and 60%, respectively.
|Table 4: Relationship between HbA1c control and treatment used for diabetes among the study group|
Click here to view
[Table 5] shows the effect of RAAS drugs on eGFR. It shows that there was no significant effect of usage of RAAS on the level of eGFR in the study group.
|Table 5: Relationship between estimated glomerular filtration rate values and usage of renin-angiotensin-aldosterone system drugs in study group|
Click here to view
| Discussion|| |
In our present study, on comparison between the results of the chosen hospitals, there was a difference in the distribution of age and sex, as age between 50 and 60 years and male sex were more at Medical Insurance Hospital, which corresponds to employee who are treated under insurance coverage.
Diabetes was better controlled in Tanta University, indicating good care of diabetes unit at Tanta University.
There were also differences among the three hospitals regarding treatment used for diabetes and usage of renin-angiotensin-aldosterone drug, which proved that the three hospitals are different in the way of management of these patients.
In our present study, 71 (27.6%) were T1DM and 186 (72.4%) were T2DM, which corresponds to the large number of patients with T2DM in Egypt.
T2DM is also the main cause of DN in France, as shown by Assogba et al. , who addressed the problem of CKD in patients with T2DM in France. They found that CKD is frequently seen in patients with T2DM and is likely to be underestimated because albuminuria screening remains inadequate. Such is the case in France, and the situation is worse in developing countries as Egypt with poor resources.
The same situation was seen in Japan, which was proved by Yokoyama et al. , who examined 17 256 diabetic patients for cumulative incidence of DN and found that the incidence of nephropathy was significantly higher (P<0.0001) in type 2 diabetic patients than in type 1 diabetic patients.
In our present study, the mean duration of diabetes till reaching stage 4 was 12.43 years (±6.388).
Our results are close to those found in Malaysia by Mostafa and Hassan , who performed a study on end stage renal disease (ESRD) diabetic patients in Sultanah Bahiyah Hospital and revealed that the mean duration of the onset of DN was 8.73 ± 3.37 and the mean duration to ESRD was 14.37 ± 4.42.
However, this was in contrast to the findings in Saudi Arabia by Alwakeel et al. , who examined 1952 diabetic patients with different stages of DN and the mean duration of diabetes was 15.4 (±7.5) years.
A low-protein diet has been investigated in patients with kidney disease including those with DN. Preclinical studies utilizing an low protein diet (LPD) have extensively analyzed its significant renoprotective effects. However, several clinical trials that analyzed LPD in kidney disease have produced disappointing results .
In our present study, good quality of diet, including LPD, low lipid level, and low glucose intake, was followed in 145 (56.4%) patients of the study group and had been proved to be positively correlated with level of control of diabetes measured by HbA1c, but the results were against the KDIGO guidelines regarding the effect on the level of eGFR.
A study completed by Meloni et al.  did not find any effect of LPD. Patients with either type 1 (n=32) or type 2 (n=37) diabetes followed a LPD (0.6 g/kg/day) or a free diet for 12 months. GFR was 45 in the free diet intake group and 43.9 in the LPD group, and at the end of study, GFR was not significantly different between groups (39.3 ml/min/1.73 m2 in the free diet intake group vs. 38.8 ml/min/1.73 m2 in the LPD group).
However, this result was against Hansen et al. , who examined the effect of LPD on 82 patients with type 1 DM with DN, and the results showed that the mean decline in eGFR was 3.9 ml/min/year (2.7–5.2) in the usual-protein diet group and 3.8 (2.8–4.8) in the LPD group. ESRD or death occurred in 27% of patients on a usual-protein diet as compared with 10% in the low-protein diet group (log-rank test; P=0.042), but the sample size seems to be small and the study was just on T1DM, which may not be conclusive; moreover, other risk factors were not excluded from the affection of eGFR.
In our present study, the target BP was achieved in 180 (70.1%) patients according to the KDIGO guidelines; 236(91.8%) patients were on treatment, and systolic and diastolic BP was proved to be correlated with good outcome of eGFR.
This level of control was highly satisfying when compared with Tomlinson et al. , who assessed level of control of BP in 49 consecutive patients with diabetes and proteinuria more tha or equal to 500 mg/24 h attending hospital diabetes clinic in the UK, and the target BP was only achieved in 16 (33%) patients.
In Germany, Schneider et al.  examined 5217 patients with DN but with stage 3 CKD, and BP was controlled only in 49.3%, but approximately the same percentage (>90%) was on treatment.
Egypt represents one of the countries that has the most prevalence of hypertesion, and our awareness and success was obvious in our results regarding the control of BP.
Our present study showed the low beneficial effect of RAAS blockage on GFR with advanced DKD, as despite using ACEi and ARBs by 134 (52.1%) patients, they showed no correlation with high GFR.
The same issue was seen with Imai et al. , who aimed to determine the effect of olmesartan therapy on renal outcomes in 577 Japanese and Chinese patients with type 2 DM and nephropathy. In this trial, olmesartan treatment did not reduce the risk of the composite renal outcome.
This was against The Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan Study trial (2001) , which was performed in 1513 patients with T2DM with nephropathy (urine protein/creatinine ≥300 mg/g and a serum creatinine level of 1.3–3 mg/dl), who were randomly assigned to losartan (50–100 mg/d) or placebo. At 3.4 years, losartan reduced the incidence of a doubling of plasma creatinine by 25% and ESRD by 28%, and losartan reduced albuminuria by 28%, whereas the placebo was associated with a 4% increase in albuminuria, but this was done only on T2DM, which could have changed if T1DM had been involved.
Therefore, the usage of RAAS blockage at advanced DKD is still controversial and still needs further studies for good evaluation of their benefits.
Despite their no effect on GFR, the use of ACEI and ARBs was shown to be correlated with good control of diabetes in our study group.
Assessment of diabetes control measured by level of HbA1c in our present study revealed that 147 (57.2%) patients had good control, where 102 (69.3%) used insulin, 16 (10.8%) used sulphonylurea and metformin, 10 (6.8%) used insulin and metformin together, six (4%) used DPP4, and six (4%) used metformin alone, five (3.4%) used sulphonylurea alone, and two (1.3%) used DPP4 with metformin.
Despite contraindication of usage of metformin according to the KDIGO guidelines, it was used in 59 (22.9%) patients.
Our results were better than the study by Kuo et al. , who assessed 1558 patients with stages 3–4 DN for outcome of HbA1c in South Taiwan, and the percentage of controlled HbA1c was 45.5%, but they did not assess the treatment used for DM.
In Malaysia, Huri et al.  assessed 242 patients with type 2 DM with DN and the majority of patients were CKD stage 4. The study revealed that DM was controlled in 42.1%, and good glycemic control was associated with use of sulphonylurea, insulin, and insulin with metformin correspondingly.
Despite contraindications of the KDIGO guidelines for usage of metformin in CKD stage 4, Dissanayake et al.  tried different doses of metformin for 18 patients and proved that metformin improved HbA1c like our study without no evidence of accumulation of metformin, no episodes of hyperlactatemia or metabolic acidosis, and no significant change in any biochemical safety measures.
The study by Lalau et al.  also on metformin proved that provided the dose is adjusted for renal function, metformin treatment appears to be safe and still pharmacologically efficacious in moderate-to-severe CKD.
All of this may lead us to more studies regarding safety of usage of metformin with advanced CKD in our community.
Assessment of lipid profile in our study group revealed that dyslipidemia was found in 127 (49.4%) patients, and of them 79 (62.2%)) patients were on no statin therapy. However, the level of cholesterol and triglycerides was not correlated with level of control of HbA1c, level of eGFR, and even usage of statins.
This was satisfactory when compared with Palazhy and Viswanathan , who assessed 89 patients with overt nephropathy for dyslipidemia in India and revealed that 75.28% had uncontrolled lipid profile.
In our present study, we demonstrated the predictors of the outcome of DN stage 4 as measured by eGFR. It revealed that male sex, high creatinine level, aging, high level of PTH, uncontrolled diastolic BP, and presence of IDA were co nsidered as predictive factors for high level of eGFR.
Zoppini et al.  evaluated the predictors of eGFR with type 2 DM, and hypertension was the only predictor, which agrees with our results; however, anemia and PTH were not seen in their study data. In contrast, obesity and level of proteinuria were seen as predictors from their data, but we unfortunately did not evaluate them.
Go et al.  in California found that proteinuria, age more than or equal to 80 years, heart failure, anemia, and higher systolic BP were the most predictors for outcome of eGFR in DN, but unlike our study, they also did not assess PTH.
| Conclusion|| |
Our patients reached stage 4 early after few years of diabetes, and the parameters that need more level of care include hypertension, diabetes, treatment used for diabetes, dyslipidemia, and acidosis.
DN is relatively common in patients with type 2 DM and is associated with other factors with adverse cardiovascular outcome. Therefore, routine screening for DKD is recommended in all patients early at the onset of diagnosis with type 2 DM.
Early assessment of care of DN stage 4 and control of modifiable risk factors, especially diet, hyperglycemia, hypertension, smoking and dyslipidemia, is essential to retard the progression of DKD.
A standard protocol of DN care needs to be submitted and followed by all hospitals in Egypt for reaching high levels of care.
Conflicts of interest
We have no conflicts of interest to disclose.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]