Management of Chronic Kidney Disease
Nurelign Abebe
Marcos Rothstein
General Principles
Definition
Chronic kidney disease (CKD) is characterized by abnormalities of kidney structure or function, present for >3 months.
These abnormalities can manifest in a variety of ways, including a reduction in clearance (GFR <60 mL/min/1.73 m2), impairment of the filtration barrier (albumin to creatinine ratio >30 mg/g), or a radiologic abnormality that reveals an underlying kidney disorder (such as polycystic kidney disease).
Most commonly, however, the term CKD is used to describe patients with a GFR <60 mL/min.
The staging of CKD depends on the level of glomerular filtration rate (GFR).
As patients progress through the stages of CKD, they develop complications associated with the loss of renal function, such as volume retention, electrolyte abnormalities, acid–base disorders, anemia, and mineral/bone disorders.
The sequelae of renal disease culminate in the development of uremia, typically at a GFR of less than 15 mL/min. Preparing each patient for end-stage renal disease (ESRD) is an important part of care in the renal clinic and will be discussed in more detail later in this textbook.
It must be kept in mind that management of CKD patients is complicated and involves close collaboration with their primary care physicians and other specialists (endocrinologists, cardiologists, vascular surgeons), as well as social workers and dieticians (please see Fig. 12-1).
Classification
The most commonly used CKD classification is based on the Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group and their Clinical Practice Guidelines for the Evaluation and Management of Chronic Kidney Disease (Fig. 12-2).1
This classification has streamlined the management of CKD, as its terminology helps the healthcare professional, as well as the patients, to clearly understand the severity of the illness and outlines the risks for disease progression, morbidity, and mortality.
Associated Conditions
Electrolyte and acid–base disorders:
With advancing CKD and decreasing GFR, the ability of the kidney to effectively eliminate the total acid load and potassium is reduced.
Acidosis typically develops with GFR below 40 mL/min.
Concomitant disorders such as diabetic nephropathy, obstructive nephropathy, sickle-cell anemia, and multiple myeloma, can cause tubular disorders which result in acidosis at earlier stages of CKD.
FIGURE 12-1. Onset of complications related to decreased GFR. This figure shows the complications of renal dysfunction in relation to GFR and stage of CKD. CKD, chronic kidney disease; GFR, glomerular filtration rate. (From Improving global outcomes (KDIGO) CKD work group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kid Int Suppl. 2013;1(3);1–150.)
Hypertension:
The pathophysiology of hypertension is multifactorial.
In CKD, the retention of sodium and water, leading to extracellular volume expansion, is a significant contributor to hypertension.
The inappropriate secretion of renin also plays a key role in the development of hypertension in CKD.
Anemia:
In patients with CKD, anemia is a common complication due to both impaired iron absorption and decreased secretion of erythropoietin.
Resistance to the action of erythropoietin also plays an important role in the development and maintenance of anemia in this patient population.
Mineral and bone disorders:
The term renal osteodystrophy had previously been used to refer to bone disorders that resulted from CKD. However, to capture the broader implications of CKD on mineral metabolism and tissue calcification, it is now known as CKD mineral and bone disorder (CKD-MBD).
With reduced GFR, a complex cascade of changes begins to occur with profound impact on mineral homeostasis and bone health. These changes include the retention of phosphorus, increased levels of fibroblast growth factor 23 (FGF23), reduced activation of vitamin D, and resulting secondary hyperparathyroidism (SHPT).
Hyperlipidemia and cardiovascular disease:
CKD is associated with increased rates of cardiovascular events, hospitalizations, and death.
FIGURE 12-2. KDIGO CKD Work Group Classification of stages of CKD. Stages of CKD based on GFR (mL/min/1.73 m2); stage 1 CKD GFR >90, stage 2 CKD 60–89, stage 3 CKD 30–59, stage 4 CKD 15–29, and stage 5 CKD <15. (From Improving global outcomes (KDIGO) CKD work group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kid Int Suppl. 2013;1(3);1–150.)
It must be noted that a significantly higher number of patients with stage 3 or 4 CKD die of cardiovascular causes before reaching the need for dialysis or transplantation.
Modification of risk factors such as hyperlipidemia, hypertension, and bone and mineral disorders is critical in reducing mortality and morbidity from cardiovascular disease.
Diagnosis
In stable CKD, estimation of the GFR is required to appropriately stage the disease. The MDRD and CKD-EPI equations are creatinine-based estimates of GFR. Their uses and limitations are discussed more thoroughly in Chapter 1 of this book.
Urine protein excretion is also a key characteristic of renal disease.
Heavy proteinuria is associated with progression of renal disease, and the amount of proteinuria serves as an indicator of the severity of disease in certain forms of glomerulonephritis.
Proteinuria can be quantified by a spot protein-to-creatinine ratio or a 24-hour urine collection for protein. Both techniques are described in Chapter 2 of this book.
A variety of diagnostic laboratory tests can be used to help evaluate the cause of CKD.
Antinuclear antibodies (ANA), antineutrophil cytoplasmic antibody (ANCA), and complement levels (C3 and C4) are frequently sent in patients who present with
features of the nephritic syndrome. In the appropriate context, HIV and hepatitis serologies are also helpful as they may contribute to renal disease manifesting in this way.
In patients with nephrotic-range proteinuria, an evaluation for nephrotic syndrome includes quantification of urine protein excretion, serum albumin, and a lipid panel.
Older patients with concomitant back pain and/or anemia should be assessed for a monoclonal gammopathy.
Serum free light chain ratios (FLC) are sensitive in detecting monoclonal gammopathies and should be ordered in patients with high index of suspicion. Although this ratio is frequently elevated in CKD patients due to reduced clearance, a kappa/lambda ratio of more than 3 in CKD patients is concerning and should prompt further workup.
Serum and urine protein electrophoresis, along with immunofixation, are also useful diagnostic tools to evaluate for paraproteinemia and related renal disorders such as light chain deposition disease, cast nephropathy, and amyloidosis.
Evaluation of anemia associated with CKD
Complete blood cell count is required at initial and subsequent office visits.
Ferritin and transferrin saturation levels are required to help guide the treatment of anemia.
The Kidney Disease Outcomes Quality Initiative (KDOQI) work group recommends a ferritin level >100 ng/mL and a transferrin saturation >20% in predialysis CKD patients.2
Some patients may respond to iron therapy even if these goals are met.
Evaluation of CKD-MBD
Parathyroid hormone (PTH), calcium, phosphorus, and 25-OH vitamin D levels should be measured to assist in directing the management of renal osteodystrophy.
For CKD stages 3 and 4, the KDOQI work group recommends maintaining corrected calcium in the “normal” range for the laboratory used and a phosphorus value between 2.7 and 4.6 mg/dL.3
The same work group recommends measurement of intact PTH every 6 to 12 months.
KDOQI recommends a target PTH level between 35 and 70 pg/mL in stage 3 CKD and a target level between 70 and 110 pg/mL in stage 4 CKD.3
Newer recommendations by the KDIGO Clinical Practice Guidelines do not endorse the use of a specific target range.4 Instead they suggest monitoring PTH trends and intervening if PTH levels are progressively rising.
Evaluation of electrolyte and acid–base disorders
A complete panel of electrolytes should be reviewed at each visit to screen for the development of hyperkalemia.
A total CO2 levels of ≥22 mEq/L is recommended for patients with a GFR <60 mL/min.
Evaluation of concomitant cardiovascular risk
A lipid panel should be checked in all CKD patients at initial office visit and annually.
The optimal low-density lipoprotein cholesterol target has not been defined for the CKD population, but given the risk for cardiovascular disease, it is generally recommended to be <100 mg/dL.Related posts:
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