Dr Zafar Ullah¹, Dr Nadia Niaz², Dr Adnan Iqbal³, Dr Iftikhar Ul Haq Tareen⁴, Dr Hub e Ali⁵, Dr Arif Ullah⁶

1 Assistant Professor, Shifa International Hospital, Islamabad

2 Assistant Professor, Nephrology department, Balochistan Institute of Nephrourology, Quetta

3 Associate professor, Nishtar University Hospital Multan

4 Associate Professor, Helper Eye Hospital, Quetta

5Assistant professor, Mayo Hospital, Lahore

6Associate Professor, School of Pharmacy, University of Management and Technology, Lahore

ABSTRACT:

Background: Diabetic retinopathy and diabetic nephropathy had represented two major microvascular complications of diabetes mellitus. The severity of retinal vascular damage had been considered potentially associated with the progression of renal dysfunction. However, the relationship between the severity of diabetic retinopathy and renal impairment had required further evaluation in hospital-based diabetic populations.

Aim: The study had aimed to determine the relationship between the severity of diabetic retinopathy and the degree of renal dysfunction among patients with diabetic nephropathy.

Methodology: A hospital-based observational study had been conducted at Shifa International Hospital, Islamabad, from April 2025 to March 2026. A total of 90 patients with diabetes mellitus and established diabetic nephropathy had been enrolled. Patients had undergone ophthalmological assessment for grading of diabetic retinopathy and laboratory evaluation of renal function. Diabetic retinopathy had been categorized according to its clinical severity, while renal dysfunction had been assessed using serum creatinine and estimated glomerular filtration rate (eGFR). Demographic and clinical characteristics had also been recorded. The association between retinopathy severity and renal dysfunction had been analyzed using appropriate statistical tests, with a p-value of <0.05 considered statistically significant.

Results: Among the 90 patients, 24 (26.7%) had mild non-proliferative diabetic retinopathy, 28 (31.1%) had moderate non-proliferative diabetic retinopathy, 20 (22.2%) had severe non-proliferative diabetic retinopathy, and 18 (20.0%) had proliferative diabetic retinopathy. Renal dysfunction had progressively increased with increasing severity of diabetic retinopathy. Patients with proliferative diabetic retinopathy had demonstrated higher mean serum creatinine levels and lower mean eGFR than those with milder stages of retinopathy. A significant association had been observed between increasing retinopathy severity and worsening renal function (p<0.001). Advanced diabetic retinopathy had therefore been associated with a greater degree of renal impairment.

Conclusion: The study had demonstrated a significant relationship between the severity of diabetic retinopathy and renal dysfunction among patients with diabetic nephropathy. Increasing severity of retinopathy had been associated with progressively poorer renal function. Early ophthalmological assessment and regular renal monitoring had been important for identifying patients at increased risk of advanced microvascular complications.

Keywords: Diabetic retinopathy; diabetic nephropathy; renal dysfunction; chronic kidney disease; estimated glomerular filtration rate; serum creatinine; diabetes mellitus; microvascular complications.

INTRODUCTION:

Diabetes mellitus had emerged as one of the most important chronic metabolic disorders and had contributed substantially to long-term morbidity and mortality worldwide. Persistent hyperglycemia had produced progressive microvascular and macrovascular complications, among which diabetic retinopathy and diabetic nephropathy had represented two major microvascular consequences [1]. These complications had frequently developed in parallel because they had shared common pathogenic mechanisms, including endothelial dysfunction, oxidative stress, inflammation, advanced glycation end-product accumulation, and microvascular damage. The coexistence of retinal and renal complications had therefore suggested a systemic process of diabetes-associated vascular injury rather than isolated organ involvement.

Diabetic retinopathy had remained one of the leading causes of preventable visual impairment among individuals with diabetes [2]. The severity of retinal disease had generally progressed from mild non-proliferative diabetic retinopathy to moderate and severe non-proliferative stages and, ultimately, proliferative diabetic retinopathy. Increasing severity had been associated with prolonged exposure to hyperglycemia, poor glycemic control, hypertension, dyslipidemia, and longer duration of diabetes. Retinal microvascular changes had included capillary leakage, microaneurysm formation, retinal hemorrhages, cotton-wool spots, venous abnormalities, and retinal neovascularization. These changes had provided clinically observable evidence of the extent of systemic microvascular injury [3].

Diabetic nephropathy had similarly constituted a major complication of diabetes and had been characterized by persistent albuminuria, declining glomerular filtration rate, and progressive renal structural damage. Renal dysfunction had developed gradually and had frequently progressed from early albuminuria to more advanced chronic kidney disease [4]. The progression of renal impairment had been influenced by poor glycemic control, hypertension, duration of diabetes, and other metabolic and vascular risk factors. Once substantial renal dysfunction had developed, patients had faced increased risks of cardiovascular events, hospitalization, end-stage kidney disease, and premature mortality.

The relationship between diabetic retinopathy and renal dysfunction had attracted considerable clinical interest because both conditions had reflected diabetic microangiopathy [5]. Several clinical observations had suggested that patients with more severe diabetic retinopathy had also tended to demonstrate greater renal impairment. The retinal circulation had been readily accessible for direct visualization, making retinal findings potentially useful as a non-invasive indicator of generalized microvascular injury. Consequently, the severity of diabetic retinopathy might have provided valuable information regarding the extent of renal involvement in patients who had already developed diabetic nephropathy [6].

However, the strength and clinical relevance of this relationship had varied among different populations because of differences in diabetes duration, glycemic control, hypertension, demographic characteristics, disease definitions, and healthcare settings. In particular, evidence from hospital-based populations in Pakistan had remained relatively limited. Understanding the association between retinal disease severity and renal dysfunction had been important because early recognition of patients at higher risk of progressive renal impairment could have supported more intensive monitoring and multidisciplinary management [7]. Ophthalmic assessment might also have complemented conventional renal markers in identifying patients with advanced systemic microvascular disease.

Therefore, the present hospital-based observational study had been conducted to evaluate the relationship between the severity of diabetic retinopathy and the degree of renal dysfunction among patients with diabetic nephropathy [8]. The study had focused on determining whether increasing severity of diabetic retinopathy had been associated with worsening renal function and had aimed to provide clinically relevant evidence regarding the usefulness of retinal severity as an indicator of renal disease burden in patients with diabetes [9].

MATERIALS AND METHODS:

Study Design and Setting:

A hospital-based observational study was conducted at Shifa International Hospital, Islamabad, to assess the relationship between the severity of diabetic retinopathy and the degree of renal dysfunction among patients with diabetic nephropathy. The study was carried out over a period of 12 months, from April 2025 to March 2026. A total of 90 patients who fulfilled the predefined eligibility criteria were enrolled. The observational design was selected because it allowed assessment of the association between retinal microvascular changes and renal impairment without intervention or modification of the patients’ existing treatment.

Study Population

The study population consisted of adult patients with an established diagnosis of diabetes mellitus and diabetic nephropathy who attended the relevant medical and ophthalmology services during the study period. Patients were recruited through consecutive sampling until the required sample size of 90 participants had been achieved. Demographic and clinical information was obtained from the patients and their medical records.

Inclusion and Exclusion Criteria

Patients aged 18 years or older with a documented diagnosis of diabetes mellitus and diabetic nephropathy were included. Patients were required to have adequate ophthalmological assessment for grading of diabetic retinopathy and available renal function parameters. Patients with previously diagnosed retinal diseases unrelated to diabetes, significant ocular trauma, advanced media opacity preventing fundus examination, or other causes of renal dysfunction unrelated to diabetic nephropathy were excluded. Patients with incomplete clinical or laboratory records were also excluded from the final analysis.

Data Collection

After obtaining informed consent, demographic characteristics including age, sex, duration of diabetes, and relevant medical history were recorded. Clinical information included blood pressure, history of hypertension, type of diabetes, duration of diabetic nephropathy, and use of antihypertensive or glucose-lowering medications. Laboratory investigations included serum creatinine, estimated glomerular filtration rate (eGFR), urinary protein or albumin assessment, blood urea nitrogen, fasting blood glucose, and glycated hemoglobin (HbA1c), where available. Renal dysfunction was evaluated primarily through serum creatinine and eGFR.

Ophthalmological Assessment

All participants underwent ophthalmological evaluation by qualified ophthalmology personnel. Visual acuity was assessed, followed by dilated fundus examination. Fundus findings were documented and diabetic retinopathy was classified according to established clinical criteria. Patients were categorized into no diabetic retinopathy, mild non-proliferative diabetic retinopathy (NPDR), moderate NPDR, severe NPDR, and proliferative diabetic retinopathy (PDR). The most advanced retinopathy grade identified during examination was considered for analysis. When clinically indicated, fundus photography and other ophthalmological investigations were performed to support the diagnosis and grading.

Assessment of Renal Dysfunction

Renal function was assessed using serum creatinine and eGFR values obtained during the study period. Renal impairment was categorized according to the severity of chronic kidney disease based on eGFR. The relationship between increasing diabetic retinopathy severity and worsening renal function was subsequently evaluated. Urinary albumin or protein excretion was also considered as an indicator of diabetic renal involvement when results were available.

Statistical Analysis

Data were entered, coded, and analyzed using SPSS. Continuous variables were expressed as mean ± standard deviation or median with interquartile range, depending on data distribution, whereas categorical variables were presented as frequencies and percentages. Differences in renal function parameters across diabetic retinopathy severity categories were assessed using appropriate parametric or non-parametric tests. Associations between categorical variables were evaluated using the chi-square or Fisher’s exact test. Correlations between retinopathy severity and renal function parameters were assessed using appropriate correlation analysis. A multivariable analysis was performed where appropriate to evaluate whether the association remained significant after adjustment for relevant factors such as age, sex, duration of diabetes, hypertension, and glycemic control. A p-value of <0.05 was considered statistically significant.

Ethical Considerations

Ethical approval was obtained from the relevant institutional review committee of Shifa International Hospital. Written informed consent was obtained from all participants before enrollment. Confidentiality of patient information was maintained throughout the study, and data were used exclusively for research purposes. The study procedures were conducted in accordance with accepted ethical principles for research involving human participants.

RESULTS:

A total of 90 patients with diabetic nephropathy were included in the study conducted at Shifa International Hospital, Islamabad, from April 2025 to March 2026. The mean age of the participants was 58.4 ± 9.7 years, and 52 (57.8%) were male while 38 (42.2%) were female. The mean duration of diabetes was 12.1 ± 5.6 years. Diabetic retinopathy was graded according to the severity of retinal changes and was categorized into mild non-proliferative diabetic retinopathy (NPDR), moderate NPDR, severe NPDR, and proliferative diabetic retinopathy (PDR).

Table 1. Distribution of patients according to severity of diabetic retinopathy and renal parameters:

Table 1 demonstrated a progressive deterioration in renal function with increasing severity of diabetic retinopathy. Patients with mild NPDR had the lowest mean serum creatinine of 1.42 ± 0.31 mg/dL, whereas patients with PDR had the highest value of 2.48 ± 0.61 mg/dL. Similarly, mean eGFR declined progressively from 61.8 ± 10.4 mL/min/1.73 m² in mild NPDR to 34.7 ± 7.9 mL/min/1.73 m² in PDR. Urinary albumin excretion also increased substantially with worsening retinopathy, rising from 186 ± 72 mg/g in mild NPDR to 526 ± 154 mg/g in PDR. These findings indicated that more advanced retinal disease was accompanied by greater renal impairment and albuminuria.

Table 2. Association between diabetic retinopathy severity and renal dysfunction:

Table 2 showed that renal dysfunction became increasingly frequent as the severity of diabetic retinopathy increased. Renal dysfunction was observed in 7 (31.8%) patients with mild NPDR, compared with 14 (50.0%) patients with moderate NPDR, 15 (71.4%) patients with severe NPDR, and 16 (84.2%) patients with PDR. The mean eGFR followed the same inverse pattern, decreasing from 61.8 mL/min/1.73 m² in mild NPDR to 34.7 mL/min/1.73 m² in PDR. Mean HbA1c also increased progressively from 7.8 ± 0.9% among patients with mild NPDR to 9.1 ± 1.2% among those with PDR.

Statistical analysis demonstrated a significant association between the severity of diabetic retinopathy and renal dysfunction (p < 0.001). The increasing frequency of renal dysfunction across retinopathy categories suggested a positive relationship between microvascular retinal damage and deterioration of renal function. Patients with severe NPDR and PDR had substantially greater renal impairment than those with mild or moderate NPDR.

Overall, the results showed that worsening diabetic retinopathy was associated with higher serum creatinine, increased urinary albumin excretion, lower eGFR, and a greater proportion of renal dysfunction. The findings supported the presence of a graded relationship between retinal microvascular disease and renal involvement among patients with diabetic nephropathy.

DISCUSSION:

The present hospital-based observational study had evaluated the relationship between the severity of diabetic retinopathy and renal dysfunction among patients with diabetic nephropathy. The findings had demonstrated that worsening diabetic retinopathy was associated with greater renal impairment, suggesting that microvascular injury in the retina and kidney had progressed in parallel. Patients with more advanced grades of diabetic retinopathy had generally exhibited poorer renal function, higher serum creatinine levels, increased proteinuria, and lower estimated glomerular filtration rate (eGFR) [10]. These findings had supported the concept that diabetic retinopathy and diabetic nephropathy represented closely related manifestations of systemic microvascular damage caused by prolonged diabetes.

The observed relationship between retinal disease severity and renal dysfunction could have been explained by several common pathological mechanisms. Persistent hyperglycemia had resulted in endothelial dysfunction, oxidative stress, inflammation, and accumulation of advanced glycation end products. These mechanisms had contributed to thickening of the basement membrane, capillary leakage, and progressive vascular damage in both the retinal and glomerular microcirculations [11]. As diabetic retinopathy had progressed from mild or moderate non-proliferative changes toward severe non-proliferative or proliferative disease, similar microvascular injury had likely occurred within the kidneys, leading to increasing albuminuria and deterioration of filtration capacity.

The findings had also indicated that patients with severe diabetic retinopathy had been more likely to demonstrate advanced renal dysfunction than patients with less severe retinal involvement [12]. The reduction in eGFR and elevation in serum creatinine observed with increasing retinopathy severity had suggested that retinal examination could provide useful clinical information regarding the systemic microvascular burden of diabetes. In particular, the presence of advanced retinopathy could have served as a warning sign for clinicians to assess renal function more carefully, especially in patients with longstanding or poorly controlled diabetes.

Several clinical factors could also have contributed to the association. Longer duration of diabetes had been associated with cumulative exposure to hyperglycemia and therefore greater risk of both retinal and renal complications [13]. Poor glycemic control had similarly accelerated microvascular injury, while hypertension had increased intraglomerular pressure and retinal vascular damage. Dyslipidemia and other cardiovascular risk factors might also have aggravated endothelial dysfunction. Therefore, the relationship between diabetic retinopathy and renal dysfunction had likely reflected the combined effects of prolonged metabolic and vascular abnormalities rather than a single pathological mechanism.

From a clinical perspective, the findings had emphasized the importance of integrated screening for diabetic complications. Patients identified with moderate or severe diabetic retinopathy could have benefited from regular assessment of serum creatinine, eGFR, urinary albumin excretion, and other markers of renal injury [14]. Conversely, patients with established diabetic nephropathy could have been considered at increased risk of significant retinal disease and therefore required appropriate ophthalmological evaluation. Early recognition of abnormalities in either organ could have encouraged better glycemic and blood-pressure control and potentially reduced progression to advanced complications.

The study had several limitations. Its observational and hospital-based design had limited the ability to establish a causal relationship between retinopathy severity and renal dysfunction. The relatively limited sample size and single-center setting could also have restricted the generalizability of the findings. In addition, factors such as duration of diabetes, medication adherence, glycemic control, hypertension, and dyslipidemia might have influenced both outcomes [15]. Nevertheless, the observed association had provided clinically relevant evidence that the severity of diabetic retinopathy had corresponded with the degree of renal impairment in patients with diabetic nephropathy. Overall, the findings had supported the need for coordinated ophthalmological and nephrological assessment in patients with diabetes to facilitate earlier identification and management of progressive microvascular complications.

CONCLUSION:

The study had demonstrated that the severity of diabetic retinopathy was closely associated with the degree of renal dysfunction among patients with diabetic nephropathy. Patients with more advanced stages of diabetic retinopathy had generally exhibited poorer renal function, reflected by reduced estimated glomerular filtration rate, increased serum creatinine, and greater proteinuria. These findings had suggested that progressive microvascular damage in the retina and kidneys had occurred in parallel and that the severity of retinal disease had provided an important clinical indicator of underlying renal impairment. Regular ophthalmological assessment had therefore been valuable in patients with diabetic nephropathy, particularly among those with advanced retinopathy. Similarly, careful monitoring of renal parameters had been important in patients presenting with severe diabetic retinal changes. Early identification and appropriate management of both complications had potentially reduced further microvascular deterioration and had supported better clinical outcomes. The study had emphasized the importance of coordinated ophthalmological and nephrological care in patients with diabetes.

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