Long-term follow-up data of living kidney donors with pre-existing pre-diabetes

INTRODUCTION

Renal transplantation is the best option for patients suffering from end-stage renal disease; transplant not only improves survival but also the quality of life when compared with dialysis. As there is a scarcity of cadaveric donors, a living donor transplant is a feasible option.^[1-4]

The global epidemic of end-stage renal disease has widened the gap between the supply and demand of living kidney donors.^[5] Thus, allowing living kidney donation using expanded donor criteria, which also allows kidney donation from donors having pre-diabetes.

We wanted to evaluate the health of the donors in long-term follow-up, those who had pre-diabetes at the time of donation.

We did a retrospective study to compare the long-term post-operative kidney functions, development of diabetes, hypertension, and proteinuria, in living donors having pre-diabetes at the time of donation, and compared the results with those donors that did not have any evidence of pre-diabetes or diabetes at our center in the past 10 years.

MATERIAL AND METHODS

Between January 2014 and December 2024, we at the Institute of Liver and Biliary Sciences, New Delhi, did 367 living donor kidney transplants. We attempted to contact all 367 donors (or donor families). Then, we filled out our questionnaire regarding current health and medications (especially diabetes mellitus [DM] drugs), current serum creatinine and HbA1c (Hemoglobin A1c) levels, urinary protein excretion, and the development of hypertension.

As per the American Diabetes Association guidelines, the definition of Pre-diabetes is an HbA1c level that ranges from 5.7 to 6.4. But to make donor criteria stricter, we took the pre-diabetes range of 5.5-6.0 for our study.

In the future, if guidelines are made, then the stricter upper limit of HbA1c can be followed in kidney donor criteria.

Study population

Inclusion criteria

All the kidney donors with no comorbidities who underwent donor nephrectomy at our center. Donors with pre-diabetes were included in our study.

Exclusion criteria

Donors with other co-existing comorbidities such as hypertension and hypothyroidism were excluded.

Pre-diabetes was not considered as an exclusion criterion.

We divided donors into two groups based on the presence of pre-diabetes in them.

We had a total of 367 donors, out of whom 65 donors were lost to follow-up, as 4 of them died and 61 were either unable or unwilling to follow up at our center. The remaining 302 donors agreeing to participate in our study were included in the data calculations [Figure 1].

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Figure 1:

Flowchart representation of the study population criteria.

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Out of these 302 donors, patients suffering from comorbidities (e.g., hypertension controlled on medication) other than pre-diabetes at the time of kidney donation were 48, and they were excluded from the study. The remaining 254 donors were divided into two groups. Group 1 included 36 donors who had pre-diabetes at the time of donation, and Group 2 included 218 donors those who had no comorbidities (no pre-diabetes also) at the time of donation. The flowchart depicts the donors.

Protocol: All the donors included in the study were called in for an outpatient department visit, and tests were done. Blood pressure was measured. The 24-h urinary was assessed for creatinine, total protein, and albumin. Blood was assessed for creatinine. The adequacy of the urine collection was determined by the total creatinine excretion. Acceptable specimens contained 1.0–2.0 g/24 h for men and 0.8–1.8 women.

To address the renal implications of pre diabetes after donation, we studied the association with incident hypertension, proteinuria, serum creatinine rise, and rate of estimated glomerular filtration rate (eGFR) change after donation between two groups of donors.

We defined proteinuria by a urinary albumin excretion rate >30 mg/g creatinine, 24 h urinary protein >200 mg/day, or ≥2+ on urine dipstick tests. To calculate the eGFR, we used the Chronic Kidney Disease Epidemiology Collaboration equation (14–15). Serum creatinine values after at least 3 months of donation were used because the goal was to model long-term trends in kidney function.

RESULTS

Renal function: Age-adjusted GFR for a solitary kidney, which was 46.8 (15.2)/1.73 m² in Group 1, and 48.2 (15.9) in Group 2, and did not have a significant difference. Cockcroft– Gault GFR was used for calculating GFR.

Urinary protein excretion: There was no difference in values for 24-h urinary protein and albumin excretion after donation between the two groups.

Blood pressure: For our study, hypertension was defined as blood pressure 140/90 mmHg or greater, or normotensive but managed with antihypertensive medication. No donors were hypertensive preoperatively. A total of 34 donors developed hypertension postoperatively, which was isolated systolic in 11 and diastolic in 4. Of the remaining 19 patients were normotensive on antihypertension medications.

Systolic blood pressure and diastolic blood pressure did not have a significant difference between Group 1 and Group 2. As 5 out of 36 donors of Group 1 developed hypertension in follow-up, out of which 4 were normotensive on antihypertension medications. Moreover, in Group 2, 29 patients out of 218 donors developed hypertension.

DISCUSSION

Our study showed that there was no significant difference in serum creatinine or 24-h urinary creatinine clearance in future follow-up of the donors who had pre-diabetes at the time of donation than those donors who did not have pre-diabetes or any other comorbidity at the time of donation. These findings of serum creatinine and 24 h urinary creatinine clearance are similar and in line with other studies that have assessed renal function >10 years after renal donation.^[6-13] In summary, our current study demonstrates that renal function is well preserved in both groups after donor nephrectomy.

In our study, urinary protein and albumin excretion were significantly higher in future follow-up in donors having pre-diabetes at the time of donation than in donors who did not have pre-diabetes or any other comorbidity at the time of donation. Many previous studies with a mean follow-up of 10–15 years^[6-13] showed similar prevalence post donor nephrectomy.

The significance of proteinuria and albuminuria in our present study is unclear, as we could not correlate increased proteinuria with any deterioration of renal function. As there was no significant difference in renal function in the follow-up period between the two groups. Moreover, as per our study, both proteinuria and albuminuria had no correlation with any deterioration of renal function.

Nevertheless, this finding suggests that patients with pre-diabetes before donation represent a subgroup at risk for the development of significant proteinuria after donation. The probable causes for proteinuria in our cases can be due to DM, hyperfiltration injury, nephrosclerosis, or new and unrelated renal disease.

There was no significant difference in the development of hypertension in our study groups. Our findings are similar to the meta-analysis and a few studies that studied the prevalence of hypertension post renal donation or nephrectomy due to other causes.^[6-13]

In our study, the development of drug or insulin-dependent diabetes was significantly higher in donors having pre-diabetes at the time of donation.

Still, the donor with pre-diabetes should not be denied from kidney donation if they are compliant enough to follow up regularly and get treated at the earliest sign of developing DM in the future. There is a lack of data regarding their long-term risks. This is evident in our study data, which show no significant difference in serum creatinine at long-term follow-up between the two groups.

Although DM has been clearly established as a major risk factor for the development of kidney disease and is the leading cause of end-stage renal disease,^[13] there are few studies examining the effects of pre-diabetes on the kidney.

The term “pre-diabetes” is applied in the setting of impaired glucose tolerance or HbA1c values between 5.5 and 6.5. They indicate a relatively high probability for the development of diabetes, microvascular, and macrovascular disease. ^[3,14,15] Studies have shown that impaired insulin sensitivity and worsening glycemic status have been associated with an increased risk of new renal dysfunction, leading to increased odds of developing chronic kidney disease in diabetic patients when compared with normoglycemic individuals.^[16-20] Although the effects of pre-diabetes in the setting of a single kidney are not known, the presence of diabetes is associated with an increased risk of developing renal disease in live kidney donors.^[21-25]

None of the studies till now have been able to prove a definite link between “pre-diabetes” and the risk of future kidney dysfunction. Suggesting that the absolute risk of developing a glycemia-related kidney abnormality in the donor having pre-diabetes was probably not high.^[26,27]

Our study showed that diabetes developed in 22% of pre-diabetic donors after a mean time of 6.2 years post kidney donation. However, there was no significant deterioration of renal function in these donors.

CONCLUSION

Pre-diabetic donors may be acceptable but require closer monitoring. As our study did not show evidence of deterioration in kidney function in them post donor nephrectomy.