**5. Pathology of CKD**

Fibrosis in the kidneys initiated by a variety of insults may not be a uniform process.

Progressive disease in diabetic patients may be related to endothelial nitric oxide deficiency with resultant endothelial dysfunction.The eventual pathology of the above mentioned series of events lead to two major histologic characteristic of CKD, focal segmental glomerulosclerosis and tubulointerstitial fibrosis. An initial insult to the kidneys will cause nephron loss.The remaining nephrons work harder to compensate for the lost nephrons

Severity and Stages of Chronic Kidney Disease 23

9. Have a nutritionist help patients maintain caloric intake. Protein restriction is difficult and may lead to malnutrition in patients with already poor appetites. We encourage protein supplementation in our CKD patients. The phosphorus level will increase, however, we try to maintain the patient's albumin predialysis or pretransplantation. Patients are started on a 2 gram potassium diet and educated about avoidance of foods high in potassium. Loop diuretics + base supplements aid in the management of hyperkalemia. Resin exchange binders are reserved for values greater than 6 as they cause diarrhea, bicarbonate loss and may worsen acidemia and further increase the

10. Education and preparation for hemodialysis or peritoneal dialysis. See if acandidate is available for transplantation. We encourage patients to have a fistula constructed after they have attended the education class and decide to do in center or home

Diabetic patients should maintain euglycemia, insulin requirements may decrease as CKD progresses. Metformin should be avoided and glipizide isthe preferred oral agentbecause it

CKD will remain a health concern into the future. CKD clinics managing patients in a coordinated fashion with nutritionists and surgeons will improve lives. Better blood pressure control with diminution of proteinuria will slow the progress of established disease. Attention to acidemia and hyperruricemia will also be beneficial. New insights into the pathogenesis and treatment of diabetes may help manage the number one cause of

[1] Primer on Kidney Disease, 5th Edition, Greenberg et al. editors, Saunders (2009).

[2] Comprehensive Clinical Nephrology, 4th edition, Jurgen Floege; Richard J. Johnson, John

[5] Tuttle, K. Relationship between cardiovascular disease and albuminuria in hypertension.

[6] Sowers J, Whaley-Connell A, Epstein M. The Emerging Clinical Implications of the Role

[7] Rennke, Helmut.Glomerular Adaptations to Renal Injury: The Role of Capillary

[8] Boor, P, Ostendorf, T andFroeje, J. Renal Fibrosis: Novel Insights into Mechanisms and Therapeutic Targets. Nature Reviews in Nephrology 6,643-656 (2011). [9] Carrero, Juan Jesus and Stenvinkel, Peter. Novel Targets for Slowing CKD Progression.

of Aldosterone in the Metabolic Syndrome and Resistant Hypertension. Annals of

Hypertension in the Pathogenesis of Focal and Segmental Glomerulosclerosis.

hemodialysis. These are patients generally in late stage 3 CKD.

is not downgraded to a metabolite excreted by the kidneys.

serum potassium value.

**6. Summary** 

**7. References** 

kidney failure in America.

Feehally

[3] Brenner and Rector's The Kidney, 8th Edition.

Internal Medicine 150,776-783(2009).

Advances in Nephrology 15,15-26(1988).

Nature Reviews in Nephrology 7,65-66(2011).

[4] Pathologic Basis of Diseases, Eighth Edition. Robins and Cotran

The Heart Institute of Spokane, Spokane, Waashington.

(compensatory hypertrophy). This leads to hemodynamic changes including glomerular hypertension and hyperfiltration. There is reduced afferent arteriolar resistance and intraglomerular pressure rises with increased filtration by the remaining nephrons. The intrinsic and extrinsic cells contribute to sclerosis as mentioned above contributing to the focal and segmental glomerulosclerosis.

Tubulointerstitial injury results from ischemia of tubule segments downstream from sclerotic glomeruli. Acute and chronic inflammation in the adjacent interstitium, and damage of pericapillary blood supply also contribute to tubular injury. The above events along with proteinuria eventually lead to tubulointerstitial fibrosis.

Angiotensin II increases vascular tone (predominantly post-glomerular) and affects intraglomerular pressure. The increased pressure alters the structure of the pores in the glomerular basement membrane (GBM) and increases proteinuria.
