Chronic kidney disease

Chronic kidney disease (CKD) is defined as an abnormality of kidney structure or function that persists for > 3 months. The most common causes of CKD in the United States are diabetes mellitus, hypertension, and glomerulonephritis. The kidney's efficient compensatory mechanisms and significant renal reserve mean that most patients remain asymptomatic until their kidney function is severely impaired. While patients are most commonly initially identified because of gradual asymptomatic elevation in serum creatinine, at advanced disease stages, patients may present with symptoms of fluid overload (e.g., peripheral edema) and/or uremia (e.g., fatigue, pruritus). Patients with CKD also have a significantly increased risk of developing atherosclerotic cardiovascular disease (ASCVD). Laboratory studies may show metabolic complications, such as hyperkalemia, hyperphosphatemia, hypocalcemia, and metabolic acidosis. The goal of management is to slow CKD progression and prevent and manage complications. This includes treatment of the underlying disease, avoiding nephrotoxic substances, maintaining adequate hydration and nutrition, reducing ASCVD risk (e.g., using statin therapy and adequate treatment of high blood pressure and/or diabetes), and addressing complications such as anemia of chronic kidney disease and CKD-mineral and bone disorder. Renal replacement therapy (i.e., dialysis or kidney transplantation) is required if CKD progresses to end-stage renal disease (ESRD).

• Prevalence ^[1]
  • An estimated 37 million individuals (15%) in the US have CKD.
  • 726,000 individuals have ESRD.
• Incidence: > 350 cases of ESRD per million individuals annually ^[1]
• Risk factors for CKD ^[1]
  • Diabetes
  • Hypertension
  • Obesity
  • Advanced age (> 60 years of age) ^[2]
  • Substance use (smoking, alcohol, recreational drugs)
  • Acute kidney injury
  • Family history of CKD
  • African American or Hispanic descent ^[3]

Epidemiological data refers to the US, unless otherwise specified.

• Diabetic nephropathy (38%)
• Hypertensive nephropathy (26%)
• Glomerulonephritis (16%)
• Other causes (15%, e.g., polycystic kidney disease, analgesic misuse, amyloidosis)
• Idiopathic (5%)

Pathophysiology depends on the underlying condition, any of which will eventually lead to progressive nephron loss, structural damage, and impaired kidney function.

Underlying conditions

• Diabetic nephropathy ^[6]
  • Hyperglycemia → nonenzymatic glycation of proteins → varying degrees of damage to all types of kidney cell.
  • Pathological changes include:
    • Hypertrophy and proliferation of mesangial cells, GBM thickening, and ECM protein accumulation → eosinophilic nodular glomerulosclerosis
    • Thickening and diffuse hyalinization of afferent and efferent arterioles/interlobular arteries
    • Interstitial fibrosis, TBM thickening, and tubular hypertrophy
• Hypertensive nephropathy: Due to protective autoregulatory vasoconstriction of preglomerular vessels, increases in systemic blood pressure do not normally affect renal microvessels. ^[7]
  • Increased systemic blood pressure (e.g., due to chronic hypertension) below the protective autoregulatory threshold → benign nephrosclerosis (sclerosis of afferent arterioles and small arteries) → ↓ perfusion → ischemic damage
  • In case BP exceeds threshold → acute injury → malignant nephrosclerosis (petechial subcapsular hemorrhages, visible infarction with necrosis of mesangial and endothelial cells, thrombosis of glomeruli capillaries, luminal thrombosis of arterioles, and red blood cell extravasation and fragmentation) → failure of autoregulatory mechanisms → ↑ damage
• Glomerulonephritis (GN)
  • Noninflammatory GN (e.g., minimal change GN, membranous nephropathy, focal segmental glomerulosclerosis)
  • Inflammatory GN (e.g., lupus nephritis, poststreptococcal GN, rapid progressive GN, hemolytic uremic syndrome)

Consequences

• Reduced GFR
  • ↓ Production of urine → ↑ extracellular fluid volume → total-body volume overload
  • ↓ Excretion of waste products (e.g., urea, drugs)
  • ↓ Excretion of phosphate → hyperphosphatemia
    • During the early stages of CKD, plasma phosphate levels will typically be normal due to the increased secretion of fibroblast growth factor 23 (FGF23). ^[8]
      • FGF23 is produced by osteoblasts in response to initial hyperphosphatemia and increased calcitriol.
      • Increased secretion of FGF23 leads to increased phosphate secretion and suppressed conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D.
      • In advanced CKD, the effects of FGF 23 subside (most likely due to development of resistance in target tissues). ^[8]
  • ↓ Maintenance of acid-base balance; → metabolic acidosis
  • ↓ Maintenance of electrolyte concentrations → electrolyte imbalances (e.g., Na⁺ retention)
• Reduced endocrine activity
  • ↓ Hydroxylation of calcifediol → ↓ production of calcitriol → (in combination with ↓ excretion of phosphate) → ↓ serum Ca²⁺ → ↑ PTH
  • ↓ Erythropoietin → ↓ stimulation of erythropoiesis
• Reduced gluconeogenesis: ↑ risk of hypoglycemia

Patients are often asymptomatic until later stages due to the exceptional compensatory mechanisms of the kidneys.

Manifestations of Na⁺/H₂O retention

• Hypertension and heart failure
• Pulmonary; and peripheral edema

Manifestations of uremia

• Definition: Uremia is defined as the accumulation of toxic substances due to decreased renal excretion. These toxic substances are mostly metabolites of proteins such as urea, creatinine, β₂ microglobulin, and parathyroid hormone.
• Constitutional symptoms
  • Fatigue
  • Weakness
  • Headaches
• Gastrointestinal symptoms
  • Nausea and vomiting
  • Loss of appetite
  • Uremic fetor: characteristic ammonia- or urine-like breath odor
• Dermatological manifestations
  • Pruritus
  • Skin color changes (e.g., hyperpigmentation, pallor due to anemia)
  • Uremic frost: uremia leads to high levels of urea secreted in the sweat, the evaporation of which may result in tiny crystallized yellow-white urea deposits on the skin.
• Serositis
  • Uremic pericarditis: a complication of chronic kidney disease that causes fibrinous pericarditis
    • Clinical features: chest pain worsened by inhalation
    • Physical examination findings
      • Friction rub on auscultation
      • ECG changes normally seen in nonuremic pericarditis (e.g., diffuse ST-segment elevation) are not usually seen.
  • Pleuritis
• Neurological symptoms
  • Asterixis
  • Signs of encephalopathy
    • Seizures
    • Somnolence
    • Coma
  • Peripheral neuropathy → paresthesias
• Hematologic symptoms
  • Anemia (caused by ↑ destruction of RBCs)
  • Leukocyte dysfunction → ↑ risk of infection
  • ↑ Bleeding tendency caused by abnormal platelet adhesion and aggregation ^[9]

Kidney OUTAGES: hyperKalemia, renal Osteodystrophy, Uremia, Triglyceridemia, Acidosis (metabolic), Growth delay, Erythropoietin deficiency (anemia), Sodium/water retention (consequences of chronic kidney disease)

Diagnostic criteria ^[5]

• Criteria for chronic kidney disease (CKD) include the persistence of eGFR < 60 mL/min/1.73 m² (≥ G3a) and/or of any of the following markers of kidney damage for > 3 months:
  • Albuminuria: e.g., urine albumin-to-creatinine ratio (UACR) > 30 mg/g (≥ A2)
  • Urine sediment abnormalities: e.g., hematuria
  • Abnormalities due to tubulointerstitial dysfunction, e.g.:
    • Electrolyte and acid-base imbalances
    • Retention of nitrogenous wastes
    • Reduced production of erythropoietin, 1,25-dihydroxyvitamin D, and/or renin
  • Histological abnormalities on biopsy
  • Imaging showing structural abnormalities: e.g., polycystic kidney disease
  • History of renal transplant
• CKD progression is the presence of either of the following:
  • A decline in renal function, leading to a change in eGFR category
  • A sustained decline in eGFR of > 5 mL/min/1.73 m² per year
• End-stage renal disease (ESRD) ; ^[10]
  • Irreversible kidney dysfunction with eGFR < 15 mL/min/1.73 m²
  • AND manifestations of uremia requiring chronic renal replacement therapy with either dialysis (hemofiltration or hemodiafiltration) or renal transplantation

CGA classification of chronic kidney disease ^[4][5]

CKD is classified according to the cause, eGFR category, and albuminuria category; this is referred to as the CGA classification.

• Clinical uses
  • Standardized documentation of CKD stages
  • Identification of CKD progression
  • Determination of the frequency of patient monitoring
• Interpretation: Higher stages correlate with a poorer prognosis. ^[11]
  • Increased risk of CKD progression and mortality (e.g., all-cause mortality, cardiovascular mortality)
  • Increased risk of developing complications (e.g., AKI, CKD-mineral and bone disorder)

Cause ^[5]

1. Systemic vs. primary cause: Determine if kidney disease is associated with a systemic disease (e.g., diabetes) or if it is primary kidney disease (e.g., polycystic kidney disease).
2. Location: Determine the location (presumed or confirmed) of the damage within the kidney.
   • Glomerular
   • Tubulointerstitial
   • Vascular
   • Cystic and congenital

eGFR and albuminuria ^[5]

The goals of the diagnostic evaluation include confirming the chronicity of kidney dysfunction and identifying the cause of kidney disease.

Approach ^[5]

• Order initial laboratory studies.
  • Determine if the patient meets the criteria for CKD.
  • Stage CKD according to the CGA classification.
  • Order further tests (e.g., electrolytes, CBC) to establish if complications are present.
• Identify the etiology of CKD and possible contributing factors.
  • Perform a comprehensive chart review, history, and physical examination.
  • Consider an initial renal ultrasound for all patients with CKD.
• Consider further investigations for specific underlying causes of CKD.

The diagnosis of CKD requires the persistence of eGFR < 60 mL/min/1.73 m² and/or of a marker of kidney damage for more than 3 months.

A rapid rise in creatinine level (i.e., over days rather than weeks or months), recent onset of uremia, and/or oliguria or anuria suggest AKI (with or without underlying CKD).

Initial laboratory studies

Parameters of renal function

• Serum markers: ↑ creatinine and BUN; (alternatively, ↑ cystatin C)
• Glomerular filtration rate: ↓ eGFR
  • Serum creatine-based eGFR (preferred): e.g., CKD-EPI equation, MDRD equation
  • Serum cystatin C-based eGFR
    • Used to confirm eGFR when creatinine-based estimation may be inaccurate or the diagnosis of CKD is in doubt ^[5]
    • E.g., CKD-EPI creatinine-cystatin C, CKD-EPI cystatin C

Urine studies

• ↑ Spot UACR: used to determine the albuminuria category for CKD staging. ^[5]
• ↑ Spot urine protein-to-creatinine ratio (UPCR): Nephrotic-range proteinuria may be seen.
• Urine dipstick: may show hematuria or proteinuria
• Urine microscopy: may show abnormal urine sediment, e.g., the presence of waxy casts

If the UPCR is significantly higher than the UACR, plasma cell dyscrasia should be suspected. Send a urine sample for protein electrophoresis to identify urine proteins other than albumin (e.g., Bence Jones protein).

Ultrasound of the kidneys and urinary tract

• First-line imaging technique for the assessment of kidney structure
• Consider obtaining for all patients to further support the diagnosis and help determine the etiology.
• Findings that suggest chronic kidney damage include: ^[12]
  • ↓ Kidney length (< 10 cm)
  • ↓ Parenchymal and/or cortical thickness
  • ↑ Cortical echogenicity
  • Cysts
  • Calcifications
• Findings that suggest specific etiologies
  • Ureteral or renal pelvic dilation suggests obstructive nephropathy.
  • Bilaterally enlarged kidneys with multiple cysts suggest polycystic kidney disease.
  • Cortical nephrocalcinosis suggests chronic glomerulonephritis or chronic pyelonephritis. ^[13]

Consider obtaining an ultrasound of the kidneys and urinary tract as part of the routine evaluation of all patients with CKD.

Additional investigations to identify underlying causes

Additional investigations should be considered based on clinical suspicion or if an underlying cause of CKD is not apparent following an initial assessment.

Integration of information from the patient's clinical presentation, laboratory tests, imaging, and in some cases, pathology, is needed to determine the underlying cause.

Noninvasive testing

Renal biopsy ^[5][14]

• Not routinely indicated
• Consider in either of the following situations:
  • Rapid and unexplained decline in eGFR
  • Need for diagnostic confirmation of the underlying etiology (e.g., glomerulonephritis) prior to initiating disease-specific therapy

Renal biopsy is only indicated in patients in whom the underlying cause of CKD is still unclear after noninvasive testing, the results are likely to influence management, and the potential benefits are thought to outweigh the risks.

The guidance below applies to patients with CKD category G1–G5 who are not on dialysis and have not had a kidney transplant.

Approach

The goals of treatment are to delay the progression of CKD and prevent and manage complications.

• Treat the underlying causes of CKD (if identified).
• Start comprehensive management.
  • Provide recommendations regarding nutrition and vaccinations, and adjust current medications as required.
  • Manage ASCVD risk factors.
  • Assess for evidence of metabolic complications and start management under specialist guidance.
• Monitor for CKD progression and continuously evaluate the need for advanced care.

If CKD progression or complications are detected during follow-up, review the current management and assess for reversible causes of progression (e.g., nephrotoxin exposure, medications affecting glomerular perfusion, urinary tract obstruction).

Pay attention to the prevention of AKI, as this may further compromise kidney function.

Nephrology consultation ^[5]

• Indications (any of the following):
  • CKD progression
  • High risk of CKD progression: i.e., eGFR category G4–G5 and/or albuminuria category A3 (macroalbuminuria)
  • Treatment-resistant hypertension or persistent hyperkalemia
  • Hematuria, nephrolithiasis, or hereditary kidney disease
  • During an AKI episode

Nutritional management ^[15]

• Fluid intake: Ensure appropriate fluid intake and avoid dehydration.
• Protein and energy consumption
  • Mediterranean diet, ↑ fruit and vegetable intake
  • Protein restriction (e.g., 0.55–0.60 g/kg/day) in patients with CKD category G3–G5
• Electrolytes
  • Sodium restriction (< 2.3 g/day): for individuals with CKD category G3–G5
  • Potassium intake adjustment: avoidance of high-potassium foods in patients with CKD category G4–G5 to reduce the risk of hyperkalemia
  • Phosphorus intake adjustment: as needed to maintain serum phosphate levels in the normal range
• Micronutrients: Consider multivitamin supplementation; for patients with inadequate dietary vitamin (e.g., vitamin D) intake. ^[15]

Dietary protein restriction must ONLY be prescribed under close clinical supervision and in consultation with a nutritionist.

Obtain a nutritionist consult for all patients with CKD.

Vaccinations

Patients with CKD are at an increased risk of vaccine-preventable infections.

• Live attenuated vaccines: Consider offering the MMR vaccine and varicella vaccine to patients who have not been vaccinated since infancy or do not have immunity.
• Non-live vaccines
  • Ensure influenza, pneumococcal, and hepatitis B vaccinations are up-to-date. ^[16]
  • See “Immunization schedule” for recommendations on indications, timing, and frequency.

Patients with CKD may be immunocompromised. Decisions regarding the use of live vaccines should therefore take into account the patient's current immune status and be made in consultation with a specialist. ^[5]

Medication management ^[5][14]

• Renally cleared medications: Adjust dosing based on the patient's eGFR (CKD-EPI equation is preferred).
• Potentially nephrotoxic substances
  • Avoid use (except when the benefits outweigh the risks).
  • Frequently monitor renal function and electrolytes and, when indicated, measure drug levels. ^[5]
  • Contrast imaging
    • The risk of contrast-induced nephropathy is highest in patients with eGFR < 30 mL/min/1.73 m².
    • For information on prevention, see “Contrast-induced nephropathy.”

Weigh the risks and benefits of potentially nephrotoxic substances on a case-by-case basis.

Given the increased risk of AKI in acutely ill patients with CKD, consider temporarily holding renally cleared medications and medications that can detrimentally affect glomerular perfusion (e.g., NSAIDs, ACEIs, ARBs).

Renal replacement therapy ^[5]

• Nonoperative (hemodialysis or peritoneal dialysis)
  • Indications include:
    • Hemodynamic or metabolic complications that are refractory to medical therapy, e.g.:
      • Volume overload or hypertension
      • Metabolic acidosis
      • Hyperkalemia
    • Serositis: e.g., uremic pericarditis
    • Other symptoms of uremia: e.g., signs of encephalopathy
    • Refractory deterioration in nutritional status
• Operative: kidney transplantation

Specific recommendations for ASCVD risk management in patients with CKD are reviewed below; see also “Hypertension,” “Lipid disorders,” “Diabetes,” and “ASCVD.”

ASCVD risk assessment

• Perform for all patients (CKD is an ASCVD risk-enhancing factor).
• Includes:
  • Diabetes mellitus screening
  • Blood pressure monitoring
  • Screening for lipid disorders
  • ASCVD risk estimation (e.g., using the 2013 ACC/AHA pooled cohort equation)

Management of ASCVD risk not only reduces cardiovascular morbidity and mortality, but also helps prevent CKD progression.

Cardiovascular disease (e.g., coronary artery disease, stroke) is the leading cause of death in patients with CKD. The risk of cardiovascular events is higher in patients with more advanced stages of CKD. ^[5]

Blood pressure control ^[17]

• Systolic blood pressure (SBP) target
  • SBP < 120 mm Hg is recommended (if tolerated). ^[17]
  • Consider higher targets (e.g., < 130–140 mm Hg) for selected patients.
• Pharmacological therapy
  • Consider for patients with SBP above target, particularly if they are in albuminuria categories A2–A3.
  • First-line therapy: RAAS inhibitors (i.e., ACEI or ARB)
    • Benefits: nephroprotection and reduced proteinuria
    • Risks: may cause hyperkalemia and/or an initial decline in GFR
  • Consider combination therapy (e.g., RAAS inhibitor PLUS a calcium channel blocker and/or a thiazide diuretic) :
    • For patients with an initial SBP ≥ 20 mm Hg above target
    • For patients who do not reach the target while on monotherapy at the optimal dose
  • Second-line agents include:
    • Loop diuretics or thiazide diuretics
    • Calcium channel blockers (CCBs)
    • Beta-blockers: usually reserved for patients with cardiovascular comorbidities
    • Aldosterone receptor antagonists: usually reserved for treatment resistant hypertension
  • See “Antihypertensive therapy” for information on medication dosages and contraindications.
• Nonpharmacological management: Recommend for all patients; see “Lifestyle changes for managing hypertension.”

Avoid any combination of an ACEI, ARB, and/or direct renin inhibitor because of the increased risk of hyperkalemia and AKI.

Good blood pressure control is essential to prevent ASCVD complications, reduce mortality, and help delay disease progression in patients with CKD.

Lipid management ^[18][19]

• Goal: reduction of ASCVD risk
• Fasting lipid panel
  • Order at diagnosis and repeat only if the results may alter management.
  • May show dyslipidemia (↑ triglycerides are common)
• Statin therapy; indications include:
  • Primary prevention of ASCVD
    • Start for all patients ≥ 50 years of age.
    • Consider for patients 18–49 years of age with concomitant diabetes mellitus and/or 10-year ASCVD risk > 10%.
  • Secondary prevention of ASCVD
  • Dyslipidemia: See “Treatment of hypercholesterolemia in adults.”
• Nonpharmacological management: Recommend as adjunctive therapy for all patients with hypercholesterolemia.

For patients with eGFR < 60 mL/min/1.73 m² (eGFR category G3–G5), adjustments to the recommended statin doses are required to reduce their potential for toxicity.

Statin therapy may be indicated regardless of serum lipid levels, as patients with CKD have a higher ASCVD risk than the general population.

Individuals with CKD often have dyslipidemia (e.g., ↑ triglycerides, ↑ LDL, ↓ HDL) due to alterations in lipoprotein metabolism.

Diabetes management ^[20]

• Glycemic target (should be individualized)
  • HbA1c of ∼ 7% is appropriate for most patients.
  • HbA1c may not accurately reflect glycemic control in patients with CKD and eGFR < 30 mL/min/1.73 m²; correlate with results from ambulatory glucose monitoring.
• Type 1 diabetes mellitus: Insulin therapy is the treatment of choice. ^[21]
• Type 2 diabetes mellitus
  • Choose first-line antihyperglycemics based on the patient's eGFR category.
    • G1–G3b: metformin PLUS an SGLT-2 inhibitor
    • G4: GLP-1 receptor agonist
    • G5: DDP-4 inhibitor
  • Periodically reassess the appropriateness of antidiabetic medications based on the patient's eGFR category.
  • See “Noninsulin antidiabetics for the treatment of T2DM” for more information.
• Nonpharmacological management: Recommend for all patients with diabetes; see “Lifestyle recommendations for patients with DM.”

SGLT-2 inhibitors and GLP-1 receptor agonists have been shown to slow CKD progression and reduce urinary albumin excretion and ASCVD events. ^[20][22]

In patients with CKD category G4–G5 who were previously on metformin and/or an SGLT-2 inhibitor, metformin should be discontinued; the SGLT-2 inhibitor may be continued if tolerated.

Antiplatelet therapy

• Usually indicated for secondary prevention of ASCVD
• May be considered for primary prevention of ASCVD in high-risk individuals (e.g., patients with CKD and diabetes) ^[5][22]

• Screening tests for complications are indicated in all patients with CKD at diagnosis to establish a baseline.
• Patients with CKD categories G3–G5 require repeat testing at regular intervals.

In CKD, close surveillance of serum potassium, calcium, and phosphate levels is essential.

Screening and periodic monitoring for complications are indicated in all patients with CKD and eGFR < 60 mL/min/1.73 m².

For recommendations on screening tests and frequencies, see “Monitoring for complications.” Specialist consultation (e.g., with a nephrologist) is advised for the management of complications.

Anemia of chronic kidney disease ^[5][25][26]

• Pathophysiology: : ↓ synthesis of erythropoietin → ↓ stimulation of RBC production → normocytic, normochromic anemia
• Laboratory findings
  • ↓ Hemoglobin (Hb)
  • MCV is usually normal.

Management

• Manage correctable causes of anemia.
  • Obtain diagnostic studies for iron deficiency.
    • Consider evaluation for underlying causes of iron deficiency (e.g., GI bleeding).
    • Consider iron therapy for iron deficiency anemia in patients with TSAT < 30% and ferritin < 500 ng/mL.
  • Check for and potentially treat vitamin B₁₂ deficiency and folate deficiency.
• Consider erythropoietin-stimulating agents (ESAs): for patients with Hb < 10.0 g/dL ; ^[26]
  • Treatment target: usually Hb concentration between 11 and 12 g/dL (without intentionally exceeding 13 g/dL)
  • Measure TSAT and ferritin at least every 3 months to determine if adjunctive iron replacement therapy is needed.
  • Adverse effects include increased risk of thrombosis, an increase in blood pressure, and headache.
• Avoid blood transfusions: particularly in patients eligible for renal transplantation (risk of alloimmunization)

Treatment with ESAs is not recommended for patients with Hb levels ≥ 10 g/dL because their use has been associated with increased mortality, stroke, and venous thromboembolism.

Chronic kidney disease-mineral and bone disorder (CKD-MBD) ^[27][28]

• Definition: abnormalities in mineral and/or bone metabolism in CKD
• Pathophysiology
  • CKD results in hypocalcemia via different mechanisms.
    • ↓ Renal excretion of phosphate → hyperphosphatemia → calcium phosphate precipitation in tissues → ↓ Ca²⁺
    • ↓ Renal hydroxylation of vitamin D → ↓ 1,25-dihydroxyvitamin D → ↓ intestinal Ca²⁺ absorption → ↓ Ca²⁺
  • Chronically decreased calcium levels can cause secondary hyperparathyroidism, which can progress to tertiary hyperparathyroidism.
• Histological classification
  • Secondary hyperparathyroidism: high turnover bone disease or osteitis fibrosa cystica; (metabolic bone disease)
  • Osteomalacia: defective bone mineralization
  • Mixed uremic bone disease: secondary hyperparathyroidism with osteomalacia
  • Adynamic bone disease: decreased bone formation without osteomalacia
• Clinical features (may be asymptomatic initially)
  • Musculoskeletal
    • Fractures
    • Bone and periarticular pain
    • Muscular weakness and pain
  • Extraskeletal
    • Focal vascular calcification (atherosclerotic plaques)
    • Diffuse vascular calcification (medial calcific sclerosis and calcific uremic arteriolopathy)
• Diagnostics ^[28]
  • Laboratory studies: frequent monitoring with a mineral and bone disorder panel
  • Imaging (not routinely indicated)
    • X-ray may show sclerotic changes (rugger jersey spine), brown tumors, and/or subperiosteal bone thinning.
    • Consider bone mineral density testing for patients with CKD category G3–G5.
• Treatment (under specialist guidance): The goal is to normalize phosphate, calcium, and PTH levels. ^[27][28]
  • Treatment of hyperphosphatemia, e.g.:
    • Dietary phosphate restriction
    • Phosphate binders (e.g., sevelamer)
  • Treatment of hyperparathyroidism, e.g.:
    • Cholecalciferol or ergocalciferol supplementation for vitamin D deficiency or insufficiency
    • Calcitriol (not routinely recommended)
    • Calcimimetics (e.g., cinacalcet)
    • Parathyroidectomy (last-line therapy)

Hyperphosphatemia, hypocalcemia, and insufficient production of vitamin D in patients with CKD may lead to secondary hyperparathyroidism and consequent renal osteodystrophy.

Growth delay and developmental delay in children

• Contributing factors include:
  • Malnutrition (protein and calorie deficit)
  • Metabolic acidosis
  • Growth hormone resistance
  • Anemia
  • Renal osteodystrophy

We list the most important complications. The selection is not exhaustive.

Chronic kidney disease in pregnancy ^[29]

• Overview
  • Prevalence of CKD in women of childbearing age is estimated to be 0.1–4%.
  • Research suggests that pregnancy negatively affects kidney function in women with CKD (as evidenced by, e.g., doubling of creatinine, progression to next stage).
  • CKD negatively influences pregnancy outcomes by increasing the risk of maternal and fetal complications (see below).
  • Physiological anatomic (e.g., dilation of the renal collecting system, changes in kidney length and volume) and hemodynamic changes (e.g., decreased mean arterial pressure) can pose a challenge to monitoring kidney function and diagnosing complications.
• Maternal complications
  • Preeclampsia
  • Concomitant hypertension and proteinuria
  • Preterm delivery
  • Cesarean delivery
• Fetal complications
  • Intrauterine growth restriction
  • Low birth weight
  • Fetal/neonatal death
• Management
  • Patients should be cared for by a multidisciplinary team, including nephrologists, neonatologists, and health care personnel specialized in high-risk obstetrics.
  • Optimization of blood pressure (i.e., < 140/90 mm Hg) to reduce the risk of preeclampsia and other complications (see “Overview of antihypertensives to avoid during pregnancy” for details)
  • Minimization of proteinuria: Treatment depends on the underlying etiology (e.g., pregnancy-safe immunosuppression with prednisone or calcineurin inhibitors in lupus nephritis).
  • Consideration of anticoagulation in individuals with severe proteinuria
  • Prevention of preeclampsia with aspirin before 16 weeks of gestation and calcium and vitamin D supplementation throughout the pregnancy

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