HEA 3071 Module 5 Chronic Kidney Disease Case Study: Estimating GFR and Slowing Decline Example

Filtering Less Every Year: Chronic Kidney Disease, a New Equation and a Trenton Patient

Student Name

B.S. in Health Studies, Thomas Edison State University

HEA-3071: Pathophysiology for Health Professionals

Mentor Name

Month Day, Year

Filtering Less Every Year: Chronic Kidney Disease, a New Equation and a Trenton Patient

The Patient

Mr. Jenkins is invented for this case. He is 57, a postal clerk in Trenton, with type 2 diabetes for fifteen years and high blood pressure. His A1C has often been above 8 percent. Recently his ankles swell by evening, and his urine looks foamy. His blood pressure is 148/90. Lab work shows a serum creatinine of 1.9 mg/dL, and his urine contains 620 mg of albumin for every gram of creatinine, well above the normal value of less than 30.

The Normal Kidney

Each kidney contains about a million nephrons. Blood enters each glomerulus, a tuft of capillaries, under pressure, and water and small solutes filter across a barrier of endothelium, basement membrane and podocytes into the tubule. The barrier normally keeps large proteins like albumin in the blood. The glomerular filtration rate, or GFR, is the total volume filtered each minute, normally above 90 mL per minute per 1.73 square meters in young adults. The tubules then reabsorb most of the water, sodium and glucose and secrete wastes.

How Kidney Disease Develops in Diabetes

High glucose damages the glomerulus in several ways. It thickens the basement membrane and expands the supporting mesangial cells. It causes the arteriole leaving the glomerulus to constrict more than the one entering, raising pressure inside the glomerulus, an effect called hyperfiltration. Raised pressure and glucose injure podocytes, and the filtration barrier begins to leak albumin into the urine. Albumin in the tubules triggers inflammation and scarring. As nephrons are lost, the remaining ones filter more to compensate, which raises their pressure and accelerates their own injury. This adaptive overwork is why chronic kidney disease tends to progress once it starts. High blood pressure adds to the damage.

Explaining His Signs

Foamy urine reflects protein leaking through the damaged barrier. Ankle swelling results from sodium and water retention by the diseased kidneys and, when protein loss is heavy, from lower albumin in the blood, which reduces the force that holds fluid in vessels. His raised creatinine reflects reduced filtration, since creatinine from muscle is cleared mainly by filtration.

Estimating GFR

GFR cannot easily be measured directly, so it is estimated from serum creatinine with an equation. Levey et al. (2009) developed the CKD-EPI equation using data from thousands of people whose GFR had been measured. It was more accurate than earlier equations at higher GFR values. It included age, sex and a coefficient for Black race, which raised the estimate for Black patients on the assumption that they have higher average creatinine levels from muscle mass.

The race coefficient drew criticism because race reflects social history rather than any measured trait of the kidney, and because a higher estimate could delay diagnosis, referral to a specialist and placement on a transplant list. Inker et al. (2021) developed new equations without race, one based on creatinine only and one combining creatinine with cystatin C, another filtration marker less affected by muscle mass. The creatinine-cystatin C equation was the most accurate, and both reduced differences between groups. The two leading U.S. kidney societies then formed a task force that urged laboratories to switch to the race-free version.

For Mr. Jenkins, the race-free equation placed his eGFR in the range of stage 3b chronic kidney disease, lower than the older equation would have reported, which led to referral to a nephrologist.

Slowing Decline

Perkovic et al. (2019) tested canagliflozin, an SGLT2 inhibitor, in the CREDENCE trial, which enrolled more than 4,400 adults whose type 2 diabetes had already damaged their kidneys enough to leak albumin all already taking an ACE inhibitor or an ARB at the highest dose they could tolerate. The trial was stopped early because canagliflozin cut the combined risk of kidney failure, a doubled creatinine, or death from renal or heart causes by about 30 percent. SGLT2 inhibitors block glucose and sodium reabsorption in the proximal tubule. The increased sodium reaching the distal tubule signals the arteriole entering the glomerulus to constrict, lowering the harmful pressure inside the glomerulus.

Matching Treatment to Mechanism

Mr. Jenkins's treatment addresses each part of the damage. An angiotensin receptor blocker relaxes the arteriole leaving the glomerulus, lowering intraglomerular pressure and albumin leakage. An SGLT2 inhibitor reduces hyperfiltration through the signal described above. Better glucose and blood pressure control reduce ongoing injury. He was also advised to avoid nonsteroidal anti-inflammatory drugs, which reduce kidney blood flow.

Social Factors

Black Americans are about three times as likely as white Americans to develop kidney failure, reflecting higher rates of diabetes and hypertension, differences in access to care and, in some families, genetic variants in the APOL1 gene. The race coefficient may have added to delays in referral.

Complications as Filtration Falls

As GFR falls, the kidneys lose functions beyond filtering. They make less erythropoietin, so red blood cell production falls and anemia develops. They activate less vitamin D and excrete less phosphate, which disturbs calcium balance and weakens bone. They excrete less potassium and acid, so potassium can rise to dangerous levels and the blood becomes acidic. Retained sodium and water raise blood pressure, which further damages the kidneys. For Mr. Jenkins, his nephrologist checked his hemoglobin, potassium, bicarbonate, calcium and phosphate and planned to watch each one as his disease progresses. Each complication follows from a specific lost function.

Limits

CREDENCE enrolled people with diabetes and substantial albuminuria. Equations estimate rather than measure GFR. Mr. Jenkins is invented, and his care illustrates principles.

Conclusion

Mr. Jenkins's kidneys have lost filtration over years of high glucose and blood pressure, and the overwork of the remaining nephrons drives further loss. Levey and colleagues' equation once raised his estimate because of his race, and Inker and colleagues' race-free equations placed him at a stage that prompted earlier specialist care. CREDENCE showed that an SGLT2 inhibitor slows the decline by easing glomerular pressure.

References

Inker, L. A., Eneanya, N. D., Coresh, J., Tighiouart, H., Wang, D., Sang, Y., Crews, D. C., Doria, A., Estrella, M. M., Froissart, M., Grams, M. E., Greene, T., Grubb, A., Gudnason, V., Gutiérrez, O. M., Kalil, R., Karger, A. B., Mauer, M., Navis, G., . . . Levey, A. S. (2021). New creatinine- and cystatin C-based equations to estimate GFR without race. New England Journal of Medicine, 385(19), 1737-1749. https://doi.org/10.1056/NEJMoa2102953

Levey, A. S., Stevens, L. A., Schmid, C. H., Zhang, Y. L., Castro, A. F., Feldman, H. I., Kusek, J. W., Eggers, P., Van Lente, F., Greene, T., & Coresh, J. (2009). A new equation to estimate glomerular filtration rate. Annals of Internal Medicine, 150(9), 604-612. https://doi.org/10.7326/0003-4819-150-9-200905050-00006

Perkovic, V., Jardine, M. J., Neal, B., Bompoint, S., Heerspink, H. J. L., Charytan, D. M., Edwards, R., Agarwal, R., Bakris, G., Bull, S., Cannon, C. P., Capuano, G., Chu, P.-L., de Zeeuw, D., Greene, T., Levin, A., Pollock, C., Wheeler, D. C., Yavin, Y., . . . Mahaffey, K. W. (2019). Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. New England Journal of Medicine, 380(24), 2295-2306. https://doi.org/10.1056/NEJMoa1811744