HYPONATREMIA AND OTHER ELECTROLYTE DISORDERS IN PATIENTS OF CHRONIC KIDNEY DISEASE OF UNKNOWN ORIGIN (CKDU): WHY ARE THEY SO DIFFERENT?

Introduction:

CKDu has witnessed a significant increase in incidence and prevalence. At our centre we see around 300 patients of CKDu annually coming from various districts of Chhattisgarh and Odisha. Hydration-electrolyte imbalance has been reported in Mesoamerican Nephropathy and from Odisha. But none of the studies to the best of our knowledge has looked into the characteristics and mechanism of electrolyte disturbances found in CKDu patients.

Methods:

OBJECTIVE

To characterise hyponatremia and electrolyte disorders in patients with CKDu.

METHODS

Cross-sectional observational study done on 103 patients of CKDu aged more than 18 years residing in the endemic zone for at least 10 years. Demographic, clinical parameters and treatment responses were recorded as per predesigned proforma. Blood and urine samples were collected after obtaining written consent. Body composition monitor (BCM) was used to check volume status.

Results:

Prevalence of CKDu in our study is 8.3%. Out of all CKDu patients, 41.5% had hyponatremia, 31.1% hypokalemia, 50.5% hypochloremia and 47.1% hypomagnesemia. Flow of study is depicted in Figure 1.  Baseline characteristics are mentioned in Table 1. Thyroid, lipid, glucose and cortisol tests were normal for all patients. None of the patients was on diuretics prior to study. All patients had a low serum osmolality and true hyponatremia. All patients except three had a chronic hyponatremia. Mean serum sodium was 126.11 ± 8.12 mEq/L. Majority patients 71.8% were asymptomatic. Blood and urine electrolytes are shown in Table 2.

Mean urine osmolality was 233 mOsm/Kg and 91.2% patients had a urine osmolality more than 100mOsm/kg indicating inappropriate secretion of Anti-diuretic hormone (ADH). The majority patients were euvolemic both clinically and by BCM analysis and further mean urine sodium was 57.27 ± 28.67 and 93.2 % patients had a urine sodium > 20mEq/L. Mean water consumption in patients of early stages of CKD was 4.3L/day and mean urine output 3.4L/day. This might be an indicator of underlying urine concentrating defect.

These findings indicate that hyponatremia occur in CKDu patients by combination of urinary sodium loss from tubular defect; decreased free water excretion due to chronically elevated ADH; and increased fluid intake relative to solute intake. Possibility of reset osmostat needs to be considered too where heat and stressful conditions daily at work might have “reset” the osmotic set point for ADH release and stimulation of thirst. As there is a clinical and biochemical phenotype of Syndrome of inappropriate diuresis (SIAD), fluid restriction and increased solute load in form of salt capsules can correct hyponatremia. Loop diuretics to increase free water excretion and potassium supplementation can also help.

87.5% patients with hypokalemia had potassium to creatinine ratio (mEq/g) >13 and 30 out of 32 hypokalemic patients have trans tubular potassium gradient TTKG >3 signifying renal potassium wasting. Coexisting electrolyte imbalances and metabolic alkalosis with low to normal blood pressure raise a possibility of acquired Gitelman phenotype.

Conclusions:

Chronically elevated ADH not only can cause hyponatremia but can potentiate kidney injury. Onset of electrolyte disorders in CKDu is as early as Stage 2 CKD which implies, an early screening of relatives can help to identify underlying urinary concentrating defects and prevent kidney disease.

I have no potential conflict of interest to disclose.

I did not use generative AI and AI-assisted technologies in the writing process.