Mild hypophosphatemia: Does it really cause muscle weakness?

I recently saw a patient with proximal muscle weakness and mild hypophosphatemia, and I wondered whether a serum phosphorous level of 2.2 mg/dL could be the cause. We know that moderate hypophosphatemia is associated with skeletal and smooth muscle dysfunction. Acute hypophosphatemia can lead to rhabdomyolysis, especially in those with chronic phosphate depletion (eg Alcoholics). Severe hypophosphatemia is associated with metabolic encephalopathy and symptoms of irritability, paresthesias, and even coma.

A pubmed search specifically looking for muscle effects of mild hypophosphatemia returned one paper. It examined respiratory muscle function in an inpatient population. The small study evaluated 23 hospitalized patients with serum phosphate levels less than 2.5mg/dl and compared them to a control group of 11 normophosphatemic inpatients. Mean age, length of stay, and number of predisposing factors for hypophosphatemia in each group was not statistically different. Mean initial serum phosphate level for the hypophosphatemic group was 1.9 +/- 0.4mg/dl compared to 3.6 +/- 0.5 mg/dl for the normophosphatemic group, with a correlating statistical difference in the measures of respiratory muscle strength. After about 2 days of repletion, the mean serum phosphate level increased in the hypophosphatemic group to 3.5 +/- 0.8 mg/dl with no difference in the respiratory muscle strength measurements after repletion in the two groups.

• 43 % (3/7) of those with phosphate levels 2.1-2.5mg/dl demonstrated muscle weakness,
• 75% (9/12) of those with phosphate levels 1.5-2.0mg/dl demonstrated muscle weakness, and all (4) of those with phosphate levels less than1.5mg/dl demonstrated muscle weakness.

Based on my brief literature search, it appears that even mild hypophosphatemia is associated with skeletal muscle weakness, and that this weakness is quickly reversible with repletion to normal levels.

Mary Lieu M.D.

Fibroepithelial polyp of the lower urinary tract

I wanted to share a case of a 35-year old man with hypertension and reduced renal function (GFR about 70). Family history was significant for a paternal grandmother and mother with hypertension. No evidence of secondary causes of hypertension including renal artery stenosis, adrenal adenomas, pheochromocytoma, etc. After further questioning a history of urinary frequency was elicited. Ultrasound was done which surprisingly showed bilateral moderate hydronephrosis. Urologic work up included urodynamic studies which showed high bladder pressures and evidence of a bladder outlet obstruction. A cystoscopy showed a possible fibroepithelial polyp (similar to one pictured).

Fibroepithelial polyp of the lower urinary tract is a rare disorder. It usually occurs in pediatric patients but may develop in adults. It is considered non-malignant and treated with a transurethral resection. They usually do not recur. The differential diagnosis also includes a urethelial papilloma and inverted papilloma, both of which are benign but require periodic surveillance for recurrence with cystoscopy. For further reading.

Race and the prediction of GFR by MDRD

The 4 variable MDRD equation was developed based on a US sample of 1628 participants in which glomerular filtration rate was measured as the renal clearance of I-iothalamate and a prediction equation was formulated using serum creatinine, age, sex, and race. For black race, the answer is multiplied by 1.2.

My question is, how well does the MDRD equation predict GFR in different global populations?

Two studies performed in sub-Saharan Africa (Ghana N=944 and South Africa N=100) comparing the MDRD and Cockcroft-Gault (CG) estimates of glomerular filtration rate (GFR) against measured creatinine clearance (24 hour urine creatinine and clearance of chromium-51-EDTA) showed that the MDRD equation performed better without using the ethnicity factor of 1.2. In a small Saudi study (N=32), GFR estimated by MDRD revealed the strongest correlation with the measured inulin clearance (r= 0.976, P= 0.0000). The correlation between eGFR and Clearance of inulin in a Japanese population (N=248) was better with the 0.881xMDRD equation than with the 1.0xMDRD study equation.

Clearly the prediction of GFR by MDRD varies by global region and most likely this variability correlates with genetic/environmental factors contributing to body muscle mass.

Hermansky-Pudlak Syndrome

This is one that Nate would have liked....I recently saw a case of renal disease in an albino Peurto Rican woman with severe pulmonary fibrosis. She holds the diagnosis of Hermansky-Pudlak Syndrome (HPS).
HPS is an autosomal recessive disorder characterized by

• Oculocutaneous albinism
• A bleeding diasthesis (absense of dense bodies)
• Sometimes pulmonary fibrosis
• Sometimes granulomatous colitis.
  

The prevalence is 1 in 500,000 in non-Puerto Ricans and 1 in 1800 in Peurto Ricans. The HPS1 gene is most associated with HPS in Peurto Ricans and for the pulmonary fibrosis which is usually fatal in 10 years from symptom onset.

The renal failure, pulmonary fibrosis, and granulomatous colitis are associated with lysosomal accumulation of amorphous lipid-protein complexes called ceroid lipofuscin. This is seen on the limited number who have undergone renal biopsy. The ceroid deposits accumulate in renal tubular epithelial cells of the proximal tubules with sparing of the glomerular epithelial cells and the distal tubular epithelium. Pathogenesis is still speculative and treatment options other than supportive care are currently unavailable.