Chronic kidney disease (newly identified): Clinical presentation and diagnostic approach in adults

INTRODUCTION — Chronic kidney disease (CKD) is defined by the presence of kidney damage or decreased glomerular filtration rate (GFR) for three or more months, irrespective of the cause (table 1) [1]. This three-month duration distinguishes chronic from acute kidney disease. Additional details on the definitions and staging are presented at length elsewhere. (See "Definition and staging of chronic kidney disease in adults" and "Definition and staging criteria of acute kidney injury in adults".)

For patients being evaluated for elevated serum creatinine or reduced estimated glomerular filtration rate (eGFR), it is important to distinguish those who have relatively stable CKD from those who have acute or subacute kidney injury, which may be ongoing and reversible. Acute kidney injury (AKI) is defined by a rise in the serum creatinine level that has developed within hours to days (table 2). Subacute kidney injury (also called acute kidney disease) informally refers to any decline in kidney function that evolves over more than 48 hours but less than three months [2]. Diagnostic approach to these patients is presented in detail elsewhere. (See "Diagnostic approach to adult patients with subacute kidney injury in an outpatient setting" and "Evaluation of acute kidney injury among hospitalized adult patients".)

An overview of the presentation and evaluation of patients with newly identified CKD is presented in this topic (algorithm 1). Specific aspects of the evaluation are presented separately:

●Assessment of kidney function by eGFR. Estimation of the GFR requires that the patient is in steady state. (See "Assessment of kidney function".)

●Careful examination of the urine by both qualitative chemical tests and microscopic examination. The urinary findings narrow the differential. (See "Urinalysis in the diagnosis of kidney disease".)

●Radiologic imaging of the kidneys. (See "Radiologic assessment of kidney disease".)

●Serologic testing and tissue diagnosis with kidney biopsy if noninvasive evaluation is insufficient for diagnosis. (See "Glomerular disease: Evaluation and differential diagnosis in adults".)

The epidemiology and management of patients with CKD, as well as clinical presentation and evaluation of CKD in children are discussed elsewhere:

●(See "Epidemiology of chronic kidney disease".)

●(See "Overview of the management of chronic kidney disease in adults".)

●(See "Chronic kidney disease in children: Clinical manifestations and evaluation".)

CLINICAL PRESENTATION — Patients with chronic kidney disease (CKD) may present with symptoms and signs resulting directly from diminished kidney function, such as edema or hypertension. However, many have no clinical symptoms, and kidney disease is often detected in these patients when an elevated serum creatinine, reduced estimated glomerular filtration rate (eGFR), or an abnormal urinalysis is discovered incidentally (when such tests are obtained as part of routine evaluation or for a possibly unrelated disorder). In addition, radiographic findings (eg, small and echogenic kidneys [by ultrasound] suggesting chronic damage, multiple bilateral kidney cysts with enlarged kidneys suggestive of polycystic kidney disease) may be observed on imaging performed for some other reason.

Depending upon the duration and severity of CKD, patients may also present with symptoms and/or signs of prolonged kidney failure, including weakness and easy fatigability, anorexia, vomiting, pruritus, and, in very advanced stages, with encephalopathy or seizures.

An abnormally reduced urine output (ie, oliguria or anuria) is seldom observed with CKD alone and always indicates at least some component of acute kidney injury (AKI). Oliguria or anuria may be present among patients with AKI superimposed on CKD, such as may be observed in a patient with chronic obstruction who develops acute urinary retention. Similarly, anuria as a result of severe or prolonged shock, bilateral urinary tract obstruction, pregnancy-related cortical necrosis, or bilateral renal arterial occlusion (eg, due to a dissecting aortic aneurysm) may occur in patients with underlying CKD. (See "Evaluation of acute kidney injury among hospitalized adult patients", section on 'Clinical manifestations'.)

The most common laboratory findings in patients with CKD include increased serum creatinine and blood urea nitrogen. Urine studies may show proteinuria (or albuminuria) and/or abnormal red or white blood cells on urine microscopy. (See "Assessment of kidney function" and "Urinalysis in the diagnosis of kidney disease".)

Other common laboratory abnormalities that may be part of the clinical picture include anemia, hyperphosphatemia, hyperkalemia, metabolic acidosis, hypocalcemia, and elevated parathyroid hormone (PTH).

The degree to which these abnormalities are present depends upon the severity of CKD. Hyperphosphatemia is uncommon among patients with CKD with eGFR >45 mL/min/1.73 m². PTH, on the other hand, may be mildly elevated even with a mild reduction of eGFR (ie, 50 to 60 mL/min/1.73 m²). (See "Overview of chronic kidney disease-mineral and bone disorder (CKD-MBD)", section on 'Overview'.)

CAUSES OF CHRONIC KIDNEY DISEASE — The most common causes of chronic kidney disease (CKD) are poorly controlled diabetes mellitus and hypertension. These and other possible etiologies are discussed in detail below. (See 'Subsequent Evaluation' below.)

The causes of kidney injury are classically divided into three categories: prerenal; intrinsic renal; or postrenal. However, any cause of kidney injury, if sufficiently severe or long-standing, may lead to persistently abnormal kidney function and therefore CKD. As an example, a patient with severe heart failure may have recurrent or prolonged acute kidney injury (AKI) due to reduced effective arterial blood volume (ie, prerenal disease). Over time, even if cardiac function and kidney perfusion pressure improve, glomerular filtration rate (GFR) may never fully recover to normal.

In addition, whatever the initial cause of kidney disease, a sustained decrease in GFR can produce adaptive hyperfiltration within the remaining functional nephrons, which may lead to further injury and worsening of CKD. (See "Overview of the management of chronic kidney disease in adults", section on 'Natural history of kidney disease' and "Secondary factors and progression of chronic kidney disease", section on 'Intraglomerular hypertension and glomerular hypertrophy'.)

INITIAL ASSESSMENT AND TRIAGE — The initial assessment for all patients who present with suspected chronic kidney disease (CKD) starts with triage of those who may need urgent dialysis based upon symptoms or life-threatening laboratory abnormalities (algorithm 1). In other patients, the time course of their kidney disease should be established to determine the role and timing of consultation with a nephrologist.

Identifying patients needing urgent dialysis — Patients with CKD may have absolute or relative indications for dialysis at the time that their kidney disease is discovered. Those who have refractory pulmonary edema, life-threatening hyperkalemia or metabolic acidosis, encephalopathy, or a pericardial rub should be referred to the emergency department for rapid evaluation and possible initiation of dialysis. These indications are discussed at length elsewhere. (See "Indications for initiation of dialysis in chronic kidney disease".)

Even among patients not requiring urgent dialysis, most may benefit from early referral to a nephrologist. (See 'Indications for a nephrology evaluation' below.)

Determine the duration of kidney disease — Among patients who do not require dialysis, we start by evaluating the duration of the kidney disease. Typically, this entails assessing serial serum creatinine values (and associated estimated glomerular filtration rates [eGFRs]) over time. If urine tests or radiologic studies of the kidney are abnormal at the time of CKD discovery, temporal changes in these data should also be assessed.  

Establishing the duration and trajectory of the disease accurately is fundamentally important and requires that older data be obtained for comparison. In some cases, it may be necessary to acquire this information from the patient's prior caregivers or from other health centers.

Along with the trend of any clinical symptoms, the trajectory of the laboratory abnormalities will determine if and when additional evaluation or nephrology referral is necessary. Recognition of a rapidly progressive process versus stable disease permits early intervention to curtail an active process and to preserve residual kidney function.  

The importance of determining the trajectory of kidney disease is illustrated by the following examples:

●Consider a patient with no significant medical history and a current serum creatinine of 4 mg/dL (354 micromol/L) who had a creatinine of 0.6 mg/dL (53 micromol/L) one month earlier. This patient has acute or subacute kidney injury. This patient needs urgent evaluation and management to stop further injury and to optimize kidney recovery. (See "Diagnostic approach to adult patients with subacute kidney injury in an outpatient setting".)

●By contrast, consider a different patient who has an identical current serum creatinine of 4 mg/dL (354 micromol/L). However, this patient has had long-standing, poorly-controlled diabetes mellitus and had a serum creatinine of 3.5 mg/dL (309 micromol/L) two years earlier, as well as chronically increased albuminuria. This patient likely has slowly progressive CKD. Although this patient will also benefit from nephrology referral, these laboratory data alone, without concurrent significant symptoms, would not justify urgent or extensive evaluation, since the process is less likely reversible. (See 'Clinical presentation' above and 'Indications for a nephrology evaluation' below.)

The determination of disease duration can also help distinguish between CKD and subacute kidney injury (also called acute kidney disease), although this distinction can be arbitrary. The clinical course of gradually progressive CKD is commonly punctuated by transient, small "spikes" in serum creatinine, which often improve to resume a prior long-term trajectory (figure 1). However, the pace of eGFR decline may increase and, if the rate of decline becomes rapid, such patients may be more appropriately evaluated as subacute kidney injury rather than CKD. (See "Diagnostic approach to adult patients with subacute kidney injury in an outpatient setting", section on 'Evaluation'.)

When prior serum creatinine values, urine studies, or radiographic images are unavailable, certain findings from the history and physical examination, or subsequent laboratory or radiographic evaluation, may suggest the duration of disease [3]. As examples:

●New symptoms or signs, such as sudden onset of anasarca and discolored urine, suggest a more acute process.

●Oliguria (urine output <0.5 mL/kg/hour [often <500 to 600 mL/day]) or anuria in a patient not on maintenance dialysis indicates an acute process. Prolonged oliguria or anuria do not occur in slowly progressive CKD (even if advanced).

●A daily increase in serum creatinine after the initial discovery of an abnormal value indicates at least some component of an ongoing acute process. Conversely, a serum creatinine that does not change, or changes minimally, over weeks to months suggests the presence of CKD. Distinguishing CKD progression from subacute kidney injury may be difficult in the setting of a serum creatinine that is worsening gradually (figure 1). The level of CKD, magnitude of eGFR decline, changes in clinical symptoms, and other factors (such as reliability of patient follow-up) should dictate the frequency of laboratory monitoring to clearly establish a trend. Overall, a rate of decrease of eGFR >5 mL/min/1.73 m² per year (or >25 percent decline in eGFR) should prompt early retesting to establish a clear trajectory and to rule out ongoing subacute injury.

●Imaging that reveals small, echogenic kidneys provides definitive evidence of chronicity of disease. However, the presence of normal-sized kidneys does not exclude chronicity, since some causes of CKD (such as diabetic kidney disease) are associated with preserved kidney size. Kidney parenchymal echogenicity (normally kidneys are less echogenic than the liver), if increased, suggests nonspecific diffuse kidney dysfunction [4-6]. (See "Radiologic assessment of kidney disease".)

●Radiologic evidence of renal osteodystrophy such as subperiosteal bone resorption or loss of bone density at the distal third of the clavicles suggests CKD. (See "Overview of chronic kidney disease-mineral and bone disorder (CKD-MBD)".)

Other findings are less helpful. As an example, anemia due to erythropoietin deficiency is a common (although not absolute) finding in CKD, but acute or subacute kidney injury can also be associated with anemia (from either hemolysis or bleeding). Although hyperphosphatemia commonly affects patients with CKD, it may also be seen in AKI or subacute kidney injury and, therefore, does not help distinguish acute from chronic disease. The absence of anemia or hyperphosphatemia does not exclude the presence of CKD.

SUBSEQUENT EVALUATION — Once the initial assessment and triage is complete, we perform an evaluation to identify the cause of chronic kidney disease (CKD) and identify individuals who may benefit from a nephrology consultation (algorithm 1).

Evaluation to identify cause — We obtain a cause-specific history, perform a targeted physical examination, and, if not done recently, we obtain urine studies and an ultrasound to determine the cause as follows:

Targeted history — We specifically determine if there is a history of any of the following:

●Long-standing diabetes and hypertension commonly lead to CKD. The duration of disease (diabetes and/or hypertension) and the degree of control should be determined in such patients. In addition, the presence of diabetic or hypertensive retinopathy should be ascertained because patients with retinopathy have a higher likelihood of having CKD from diabetes and/or hypertension. (See "Clinical features, diagnosis, and treatment of hypertensive nephrosclerosis" and "Diabetic kidney disease: Pathogenesis and epidemiology" and "Overview of hypertension in acute and chronic kidney disease".)

●Renovascular disease should be suspected among patients who have peripheral arterial disease in other vascular beds or who have multiple vascular risk factors, such as age over 50 years, hyperlipidemia, or cigarette smoking. Renovascular disease can present as CKD. Features that suggest CKD due to renovascular disease include resistant hypertension, recurrent flash pulmonary edema, or a reversible increase in serum creatinine after receiving antihypertensive therapy, particularly angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), which improves after withdrawal of the drug. (See "Chronic kidney disease resulting from atherosclerotic renal artery stenosis".)

●Patients should be asked about a history of prior severe or prolonged acute kidney injury (AKI) to determine if it could have contributed to their CKD. Prior AKI, particularly if dialysis-requiring, may lead to CKD. CKD may have developed even if the patient had sufficient recovery to stop dialysis. (See "Kidney and patient outcomes after acute kidney injury in adults", section on 'Determinants of kidney outcomes'.)

●Histories of obesity, heart failure, liver failure, autoimmune disease, recurrent and complicated urinary tract infections, and reduced kidney mass (eg, nephrectomy, renal agenesis) should be elicited due to their associations with CKD. (See "Overweight and obesity in adults: Health consequences", section on 'Chronic kidney disease' and "Cardiorenal syndrome: Definition, prevalence, diagnosis, and pathophysiology" and "Hepatorenal syndrome" and "Lupus nephritis: Diagnosis and classification" and "Overview of and approach to the vasculitides in adults".)

●Inherited disorders, such as some cystic, interstitial, and glomerular kidney diseases, are relatively common causes of CKD. Thus, it is important to ask specific questions about kidney disease in family members, including their history of abnormal kidney imaging (eg, large kidneys with many cysts seen in polycystic kidney disease) or abnormal urine studies (eg, hematuria or proteinuria found in glomerular diseases). (See "Autosomal dominant polycystic kidney disease (ADPKD) in adults: Epidemiology, clinical presentation, and diagnosis" and "Autosomal dominant tubulointerstitial kidney disease" and "Focal segmental glomerulosclerosis: Genetic causes" and "Fabry disease: Kidney manifestations" and "C3 glomerulopathies: Dense deposit disease and C3 glomerulonephritis", section on 'Pathogenesis' and "IgA nephropathy: Pathogenesis", section on 'Genetic susceptibility'.)

●Patients who have a history of cancer (eg, myeloma or renal cell carcinoma) and treatment with chemotherapy or radiotherapy may develop CKD from the cancer itself or from its treatment. Many patients with multiple myeloma, for example, have AKI at the time of diagnosis; such patients often develop CKD as a result of incomplete recovery from AKI. Patients with renal cell carcinoma often require a partial or complete nephrectomy, which can lead to CKD from decreased kidney mass. In addition, patients who are treated with chemotherapy using cisplatin, ifosfamide, immune checkpoint inhibitors, or newer molecular-targeted agents may develop CKD as an adverse consequence of their treatment. (See "Overview of kidney disease in patients with cancer" and "Kidney disease in multiple myeloma and other monoclonal gammopathies: Etiology and evaluation" and "Nephrotoxicity of molecularly targeted agents and immunotherapy" and "Cisplatin nephrotoxicity" and "Ifosfamide nephrotoxicity".)

●Urinary tract obstruction should be suspected among patients who have a history of prior urological surgery, prior pelvic or retroperitoneal surgery, a known or suspected abdominal or retroperitoneal malignancy, neurologic disease involving the bladder, gross hematuria, lower abdominal, pelvic, or flank pain, or in men with lower urinary tract symptoms. (See "Clinical manifestations and diagnosis of urinary tract obstruction (UTO) and hydronephrosis" and "Chronic urinary retention in females" and "Lower urinary tract symptoms in males".)

●Clinicians should inquire about risk factors for human immunodeficiency, hepatitis C, or hepatitis B virus infections, such as a history of intravenous drug use or sexually transmitted disease. Patients with risk factors should be tested for the presence of these viruses. Because these viruses may cause a variety of kidney diseases, these etiologies should also be considered when the underlying cause of CKD is not clear. (See "Overview of kidney disease in patients with HIV" and "Kidney disease associated with hepatitis B virus infection" and "Overview of kidney disease associated with hepatitis C virus infection".)

●Medications should be reviewed, including for potentially nephrotoxic medications that the patient used in the past (even if not currently using). As examples, prolonged use of lithium for psychiatric conditions, certain Chinese herbs from "slimming clinics," or analgesic combination agents may each cause chronic interstitial injury that leads to CKD. In addition, drugs that can precipitate allergic interstitial nephritis may lead to CKD since such patients often do not have complete recovery of kidney function. (See "Renal toxicity of lithium" and "Nephropathy induced by aristolochic acid (AA) containing herbs" and "Clinical manifestations and diagnosis of analgesic nephropathy".)

●Geography may be a clue to the cause of CKD. A history of agricultural work in hot environments or history of exposure to pesticides and other agrochemicals is associated with CKD of unknown cause (ie, "CKDu," also called Mesoamerican nephropathy). Such a history should raise suspicion for this disorder as the cause of CKD. Patients who lived for many years in particular regions of the Balkans may be at risk for a different chronic tubulointerstitial nephropathy that is slowly progressive. In endemic regions, infections such as schistosomiasis and tuberculosis may be common causes of CKD. (See "Mesoamerican nephropathy" and "Balkan endemic nephropathy" and "Schistosomiasis and glomerular disease" and "Urogenital tuberculosis".)

●A review of toxic environmental or occupational contaminants may reveal exposure to lead, which is associated with CKD. A history of lead mining, plumbing, auto-repair work, or shipbuilding may be associated with significant lead exposure. (See "Lead nephropathy and lead-related nephrotoxicity".)

Targeted physical examination — We perform a physical exam to elicit the following signs that may suggest a specific etiology of kidney disease:

●Signs of volume overload may indicate the presence of heart failure or cirrhosis, which are associated with CKD.

●Signs of volume depletion, such as may occur with a chronic diarrheal syndrome or a high-output bowel stoma, may suggest a longstanding state of prerenal azotemia with risk of recurrent AKI, thereby leading to CKD.

●The presence of arteriovenous nicking or retinopathy on funduscopic examination can be seen in chronic hypertensive microvascular disease (image 1), which may also involve the kidney.

●An abdominal bruit or abnormal distal pulses may be detected in patients with renal artery stenosis.

●Enlarged kidneys that are palpable on examination may suggest polycystic kidney disease.

●Peripheral neuropathy may be associated with diabetic microvascular disease or another disorder that causes dysautonomia (such as a paraproteinemia).

●Rashes and skin lesions, such as may occur with leukocytoclastic vasculitis or purpura, suggests that small vessel vasculitis may be the cause of CKD (picture 1 and picture 2).

●Skin thickening and hardening as may be seen with systemic sclerosis (scleroderma), an uncommon cause of CKD (figure 2 and picture 3).  

Targeted laboratory assessment — Initial testing for all patients should include:

●Basic metabolic panel that includes serum creatinine for calculation of the estimated glomerular filtration rate (eGFR).

●Complete blood count with white cell differential ("CBC with diff").

●Urinalysis using reagent test strips (dipstick) and automated urine microscopy.

●If an experienced operator is available for manual review of urine microscopy, such a detailed examination of the urine may further guide the evaluation. Urine microscopy is especially helpful if there are cellular elements (red blood cells and/or white blood cells), cellular or granular casts, or crystals in the urine. In the absence of an experienced urine microscopist, or if the urinalysis and automated microscopy are normal, manual review may generally be deferred. (See "Urinalysis in the diagnosis of kidney disease".)

●Quantification of urine protein and albumin by random (or "spot") protein-to-creatinine ratio (UPCR) and albumin-to-creatinine ratio (UACR); each provides slightly different but related information. Our practice is to check both UPCR and UACR concurrently, and, in some cases, a 24-hour urine collection for protein and creatinine at least once early in the evaluation and to follow one of the values over time. A more detailed discussion of proteinuria is presented elsewhere. (See "Assessment of urinary protein excretion and evaluation of isolated non-nephrotic proteinuria in adults".)

●In addition, in patients older than 40 years of age who have hypercalcemia, severe anemia, bony lesions suggestive of multiple myeloma, or a progressively worsening eGFR without an obvious cause, we also obtain a serum and urine protein electrophoresis with immunofixation and a serum free light chain assay. (See "Kidney disease in multiple myeloma and other monoclonal gammopathies: Etiology and evaluation", section on 'Evaluation'.)

Specific abnormalities in blood and urine studies guide the utility and timing of further evaluation and referral. In addition to a rapidly declining eGFR, other laboratory abnormalities may require directed evaluation and management by a nephrologist. As an example, microscopic hematuria and/or increased proteinuria (as detected by UPCR or UACR) often prompts specific serologic testing to investigate possible glomerular disease. Sterile pyuria, especially if coupled with peripheral eosinophilia, may direct further testing for a hypersensitivity reaction or autoimmune disease or, in endemic regions, renal tuberculosis. The combination of metabolic acidosis with hyper- or hypokalemia may indicate the presence of a renal tubular acidosis, which is a notable feature in some etiologies of CKD. Evidence of a monoclonal gammopathy should prompt a referral to nephrology or hematology for further evaluation of related kidney or plasma cell diseases. (See 'Indications for a nephrology evaluation' below and "Clinical manifestations and diagnosis of acute interstitial nephritis" and "Glomerular disease: Evaluation and differential diagnosis in adults" and "Kidney disease in primary Sjögren's disease" and "Kidney disease in sarcoidosis" and "Urogenital tuberculosis", section on 'Renal and urologic tuberculosis' and "Kidney disease in multiple myeloma and other monoclonal gammopathies: Etiology and evaluation" and "Renal amyloidosis" and "Membranoproliferative glomerulonephritis: Classification, clinical features, and diagnosis", section on 'Monoclonal gammopathies'.)

Depending upon further testing by a nephrologist, a kidney biopsy may be warranted. (See 'Indications for a nephrology evaluation' below.)

In some cases of newly identified CKD with stable, mild laboratory abnormalities, expectant management with watchful waiting, and without nephrology referral, is reasonable. A patient, for example, with stable eGFR >45 mL/min/1.73 m², normal urine microscopy, UPCR <500 mg/g and UACR <300 mg/g may not require extensive serologic testing or kidney biopsy. (See 'Stable patients not in need of a nephrology evaluation' below.)

Targeted radiologic assessment — Unless recent abdominal imaging is available, we obtain a kidney ultrasound in all patients at the time of their initial evaluation for CKD. Abnormalities in kidney imaging may warrant urologic evaluation and urodynamic studies. (See "Radiologic assessment of kidney disease".)

Patients who have evidence of urinary tract obstruction (ie, hydronephrosis) on ultrasound require further investigation to determine the cause and duration, and to establish reversibility of kidney injury. Early recognition and correction of urinary obstruction can help salvage kidney function. (See "Clinical manifestations and diagnosis of urinary tract obstruction (UTO) and hydronephrosis".)

Patients who are at a high risk for renovascular disease should have dedicated imaging to evaluate for renal artery stenosis. Vascular duplex ultrasound of the renal arteries is often a first step. Depending upon each institution's radiologic expertise, computed tomography angiography and/or magnetic resonance angiography may be obtained. This imaging is used in conjunction with vascular surgery or interventional radiology evaluation to determine the possible role of revascularization versus medical management. (See "Chronic kidney disease resulting from atherosclerotic renal artery stenosis".)

Indications for a nephrology evaluation — Based upon the targeted history, physical examination, laboratory testing, and imaging discussed above, further evaluation with additional tests and kidney biopsy may be warranted. (See "Definition and staging of chronic kidney disease in adults", section on 'Referral to a specialist' and "Overview of the management of chronic kidney disease in adults", section on 'Referral to nephrologists'.)

With increasing accessibility of telehealth visits and electronic consults that can often be completed more efficiently than traditional in-office patient visits, a subspecialty referral may now include a spectrum of possible scenarios. In some cases, a nephrologist may review the electronic medical record for the history, medications, and laboratory data and determine that a formal referral for full evaluation is appropriate. In other cases, she or he may simply render education and guidance to a primary care clinician on further evaluation, if necessary, and on issues of surveillance and management of stable disease. Local practice may vary along this spectrum. In an adult with newly identified CKD, indications for consultation with a nephrologist include:

●eGFR <30 mL/min/1.73 m²

●Persistent UACR ≥300 mg/g (34 mg/mmol)

●Persistent UPCR ≥500 mg/g (56.5 mg/mmol)

●Abnormal urine microscopy (cellular casts, nonurologic hematuria, sterile pyuria)

●Personal history of systemic autoimmune disease

●Large cystic kidneys by kidney imaging or examination

●Known history of multiple myeloma or monoclonal gammopathy

●Evidence of relatively rapid loss of kidney function (reduction in eGFR >5 mL/min/1.73 m² per year or decline >25 percent); because there is common physiologic variability, repeat lab testing within one to two months (or sooner in some cases) may be warranted to clearly establish trajectory of eGFR change (figure 1)

●Single kidney with eGFR <60 mL/min/1.73 m²

●Inability to identify a presumed cause of CKD, especially in younger patients

●Difficult to manage laboratory abnormalities such as hyperkalemia, metabolic acidosis, anemia requiring erythropoietin therapy, hyperphosphatemia, or hypocalcemia

●Resistant hypertension

●Recurrent or extensive nephrolithiasis

●Pregnancy

●Confirmed or presumed hereditary kidney disease, such as polycystic kidney disease, Alport syndrome, or autosomal dominant interstitial kidney disease

●Difficult to manage complications of various medications, such as chemotherapeutic agents that may cause kidney injury or increase proteinuria

Other patients do not require nephrology evaluation. As an example, patients who have an eGFR that does not change over sequential measurements, who have minimal or no proteinuria, and who have absence of cellular elements on urine microscopy undergo a limited evaluation. A kidney biopsy is rarely performed in such patients and the cause of CKD may not be identified with certainty. (See 'Stable patients not in need of a nephrology evaluation' below.)

Stable patients not in need of a nephrology evaluation — Many patients will have the cause of their kidney disease become apparent with the evaluation described above. (See 'Evaluation to identify cause' above.)

However, the cause may not be apparent in some despite a thorough evaluation. Among such patients, further evaluation and management depends in part upon whether the kidney disease is progressive or stable. We monitor serum creatinine within six weeks after CKD was initially recognized. In some cases, the test should be repeated even sooner to determine if there is evidence of rapid progression (ie, an eGFR decline of >5 mL/min/1.73 m² per year or decline >25 percent). Those with rapid progression need to be evaluated by nephrology. (See 'Indications for a nephrology evaluation' above.)

Patients who have stable, mild to moderate kidney disease (ie, that is not progressive) can be monitored every three to six months (or a longer interval if laboratory studies and clinical status are clearly stable) for the development of the following findings that would benefit from a nephrology evaluation (see 'Indications for a nephrology evaluation' above):

●A decline in the eGFR to <30 mL/min/1.73 m².

●A persistent increase in either the UACR to ≥300 mg/g (34 mg/mmol) or the UPCR to ≥500 mg/g (56.5 mg/mmol).

●Development of new clinical evidence of autoimmune disease or monoclonal gammopathy. This may be detected by new rash, arthritis, bone pain, cytopenias, or other clinical changes that are otherwise unexplained and were not present at initial evaluation.

●A change in the pace of eGFR decline, such that the patient is rapidly losing kidney function (ie, loss of eGFR >5 mL/min/1.73 m² per year or >25 percent decline in eGFR).

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Chronic kidney disease in adults".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Chronic kidney disease (The Basics)" and "Patient education: Acute kidney injury (The Basics)")

●Beyond the Basics topics (see "Patient education: Chronic kidney disease (Beyond the Basics)" and "Patient education: Dialysis or kidney transplantation — which is right for me? (Beyond the Basics)" and "Patient education: Hemodialysis (Beyond the Basics)" and "Patient education: Peritoneal dialysis (Beyond the Basics)" and "Patient education: Protein in the urine (proteinuria) (Beyond the Basics)" and "Patient education: Split urine collection for orthostatic proteinuria (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Chronic kidney disease (CKD) versus acute kidney disease or injury – CKD is defined by the presence of kidney damage or reduced glomerular filtration rate (GFR) for three or more months, irrespective of the cause (table 1). Subacute kidney injury (also called acute kidney disease) informally refers to any decline in kidney function that evolves over more than 48 hours but less than three months. Acute kidney injury (AKI) is defined by a rise in the serum creatinine level that has developed within hours to days (table 2). (See 'Introduction' above and "Diagnostic approach to adult patients with subacute kidney injury in an outpatient setting" and "Evaluation of acute kidney injury among hospitalized adult patients".)

●Clinical presentation – Patients with CKD may present with symptoms and signs resulting directly from diminished kidney function, such as edema or hypertension. However, many have no clinical symptoms, and kidney disease is often detected in these patients when an elevated serum creatinine, reduced estimated GFR (eGFR), or an abnormal urinalysis is discovered incidentally (when such tests are obtained as part of routine evaluation or for a possibly unrelated disorder). In addition, radiographic findings (eg, multiple bilateral kidney cysts with enlarged kidneys suggestive of polycystic kidney disease) may be observed on imaging performed for some other reason. (See 'Clinical presentation' above.)

●Initial assessment and triage – The initial assessment for patients who present with suspected CKD starts with triage of those who may need urgent dialysis based upon symptoms or life-threatening laboratory abnormalities (algorithm 1).

•Identification of patients needing urgent dialysis – Patients who have refractory pulmonary edema, life-threatening hyperkalemia or metabolic acidosis, encephalopathy, or a pericardial rub should be referred to the emergency department for rapid evaluation and possible initiation of dialysis. (See 'Identifying patients needing urgent dialysis' above.)

•Evaluation of disease duration – Among patients who do not require dialysis, we start by evaluating the duration of the kidney disease. Typically, this entails assessing serial serum creatinine values (and associated eGFRs) over time. If urine tests or radiologic studies of the kidney are abnormal at the time of CKD discovery, temporal changes in these data should also be assessed. Establishing the duration and trajectory of the disease accurately is fundamentally important and requires that older data be obtained for comparison. In some cases, it may be necessary to acquire this information from the patient's prior caregivers or from other health centers. When prior serum creatinine values, urine studies, or radiographic images are unavailable, certain findings from the history and physical examination, or subsequent laboratory or radiographic evaluation, may suggest the duration of disease. (See 'Determine the duration of kidney disease' above.)

●Subsequent evaluation – Once the initial assessment and triage is complete, we perform an evaluation to identify the cause of CKD and identify individuals who may benefit from a nephrology consultation (algorithm 1).

•Evaluation to identify cause – We obtain a cause-specific history, perform a targeted physical examination, and, if not done recently, we obtain urine studies and an ultrasound to determine the cause. (See 'Evaluation to identify cause' above.)

•Indications for a nephrology evaluation – Based upon the targeted history, physical examination, laboratory testing, and imaging, further evaluation with additional tests and kidney biopsy may be warranted. Some adults with newly identified CKD should be referred to a nephrologist. (See 'Indications for a nephrology evaluation' above.)