When Diabetes Comes for the Kidneys, Blood Chemistry Tells the Story First

One in three adults in Pakistan now has diabetes. That figure, confirmed by the World Health Organization last November, makes the country’s rate the highest in the world in percentage terms, outpacing even China and India in sheer proportion of its population affected. Most people on the planet who get diabetes will never develop kidney failure from it. But somewhere between 20 and 30 percent will, and in Pakistan, where healthcare access is patchy, incomes are low and diagnoses often come late, those odds loom large.

A team of researchers based in Sindh province has been trying to get ahead of that trajectory. Abdul-Rehman Phull and colleagues at Shah Abdul Latif University in Khairpur spent the better part of 2023 drawing blood from 200 people, 50 in each of four carefully defined groups: patients whose diabetes had already damaged their kidneys, patients with diabetes but healthy kidneys, people with kidney disease unrelated to diabetes, and a set of healthy controls.

Their goal was not to discover a new biomarker or test some experimental drug. It was, in a way, more fundamental than that. They wanted a detailed biochemical portrait of what diabetic nephropathy actually looks like at the molecular level compared with diabetes alone, kidney disease alone, and normal health, in a population where this kind of granular data barely exists. The results, published in January in Exploratory Research and Hypothesis in Medicine, reveal a tangle of metabolic disturbances that are more complex (and in places more counterintuitive) than a simple story of high sugar wrecking the kidneys.

Start with the glucose numbers, which behave roughly as you’d expect. Fasting blood sugar in the diabetic nephropathy group averaged about 179 mg/dL, well above normal, and their glycated haemoglobin sat at 8.1 percent, indicating months of poor control. The diabetes-only group, though, actually had the wildest random glucose readings: 280 mg/dL on average, significantly higher than the kidney-damaged patients.

Then things get less predictable. You might assume that patients whose diabetes has progressed to kidney failure would show the worst lipid profiles, clogged with cholesterol and triglycerides. They didn’t. The diabetes-only group had the highest levels of LDL cholesterol, triglycerides, and total cholesterol across all four groups. The diabetic nephropathy patients, by contrast, recorded the lowest lipid concentrations of anyone in the study, including healthy controls for some measures. The paper doesn’t offer a clear explanation for the pattern, though advanced kidney disease is known to disrupt lipid metabolism in ways that don’t always mirror the dyslipidemia seen in diabetes alone.

Where the kidney-damaged patients did stand apart was in the waste products building up in their blood. Creatinine in the diabetic nephropathy group averaged 5.67 mg/dL; a healthy person typically clocks in below 1.2. Blood urea nitrogen hit 72 mg/dL, roughly six times normal. These are the chemical signatures of kidneys that can no longer filter properly, their glomeruli damaged by prolonged exposure to high glucose.

Inflammation told its own, somewhat surprising story. C-reactive protein, a marker of systemic inflammation, was elevated in both the nephropathy groups but not particularly in the diabetes-only patients. And lactate dehydrogenase, an enzyme that spills out of damaged cells, was highest not in the diabetic kidney patients but in the non-diabetic nephropathy group, where it reached a striking 1,216 U/L. That is roughly three and a half times the level seen in healthy controls. Previous research has linked elevated LDH in kidney disease patients to increased risk of cardiovascular death, so its prominence in non-diabetic nephropathy hints at tissue damage pathways that operate independently of blood sugar.

The study has obvious limitations. Two hundred participants from a single institute in rural Sindh is a small window onto a very large problem. Medication use, dietary detail and disease duration were not fully controlled for. The researchers acknowledge as much.

But what makes this work matter is context. Pakistan has roughly 33 to 36 million people living with diabetes, depending on which estimate you favour, and the numbers have climbed by 40 percent in the past five years alone. Diabetic nephropathy is the leading cause of chronic kidney disease in the country, according to epidemiological reviews. Yet much of the country’s clinical research infrastructure sits in urban centres like Karachi and Lahore; rural Sindh, where most people earn less than $3 a day, has far less of it. The idea that a university lab in Khairpur is building biochemical profiles of its own population, tailored to its own clinical reality, is itself quietly significant.

The bigger picture, perhaps, is what this kind of baseline data could eventually enable. Standard biomarkers like creatinine and albumin often catch kidney damage only after significant structural harm has already occurred. Researchers worldwide are hunting for earlier signals, molecules like NGAL and KIM-1 that might flag trouble before filtration collapses. But you can’t interpret novel biomarkers without first understanding the conventional biochemical landscape of your patient population, and for rural Pakistan, that groundwork is still thin.

Phull’s team call for longitudinal studies that track how these biochemical parameters shift over time in diabetic patients, the sort of work that could, eventually, tell clinicians which patients are sliding toward nephropathy before the kidneys visibly fail. In a country where, as the WHO’s representative in Pakistan put it last November, diabetes remains a silent killer, catching kidney damage early could make the difference between a manageable chronic condition and dialysis.

Study link: https://www.xiahepublishing.com/2472-0712/ERHM-2025-00033