Yellow zone Nefroloji / Glomerüler Hastalıklar

IgA Nephropathy — Hematuria Starts at the Same Time as Infection and the 'Benign' Label Conceals Its Thirty-Year Course

IgA nephropathy is THE MOST COMMON PRIMARY GLOMERULAR DISEASE IN THE WORLD, and its CLASSIC PRESENTATION DIRECTLY PROVIDES THE DIAGNOSIS: VISIBLE HEMATURIA THAT EMERGES DURING THE SAME DAYS AS AN UPPER RESPIRATORY TRACT INFECTION.

Timing is distinctive: in this disease, hematuria occurs simultaneously with the infection, whereas in post-streptococcal glomerulonephritis, hematuria occurs weeks after the infection (relevant protocol); THIS DISTINCTION CAN BE MADE IN THE HISTORY WITH A SINGLE QUESTION. THE DISEASE'S SPECTRUM OF PRESENTATION IS VERY BROAD:

IT RANGES FROM INCIDENTAL MICROSCOPIC HEMATURIA TO RAPIDLY PROGRESSIVE RENAL FAILURE. THE MOST COMMON MISTAKE IS TO LABEL A YOUNG PATIENT WITH ISOLATED MICROSCOPIC HEMATURIA AS 'BENIGN' AND DISCONTINUE FOLLOW-UP:

FOR MOST OF THESE PATIENTS THE COURSE IS GOOD, BUT SOME PROGRESS TO END-STAGE RENAL FAILURE OVER DECADES, AND A PATIENT DIAGNOSED AT TWENTY-FIVE YEARS OLD MAY REQUIRE DIALYSIS AT FIFTY; THIS EXPLAINS WHY FOLLOW-UP NEEDS TO BE LIFELONG. THE BASIS OF TREATMENT IS SUPPORTIVE THERAPY THAT REDUCES PROTEINURIA AND CONTROLS BLOOD PRESSURE, AND IMMUNOSUPPRESSIVE THERAPY IS NOT INITIATED UNTIL THIS THERAPY IS OPTIMIZED.

SECONDARY CAUSES SHOULD BE INVESTIGATED. ALL DOSAGES SHOULD BE VERIFIED FROM THE INSTITUTIONAL PROTOCOL.

Rapid management

CLASSIC PRESENTATION:
VISIBLE HEMATURIA THAT APPEARS ON THE SAME DAYS AS AN UPPER RESPIRATORY TRACT INFECTION; bleeding LASTS FOR A FEW DAYS, RESOLVES SPONTANEOUSLY, and MAY RECUR.
TIMING IS DISTINGUISHING:
IN THIS DISEASE, BLEEDING IS CONCURRENT WITH THE INFECTION ("my urine became dark when my throat was sore"), whereas in POST-STREPTOCOCCAL GLOMERULONEPHRITIS, it occurs WEEKS AFTER THE INFECTION (relevant protocol) → IN HISTORY, ONLY ONE QUESTION MAKES THE DIFFERENCE.
OTHER FORMS OF PRESENTATION:
ACCIDENTALLY FOUND MICROSCOPIC HEMATURIA and PROTEINURIA, NEPHROTIC-LEVEL PROTEIN LOSS (relevant protocol), HIGH BLOOD PRESSURE, CHRONIC KIDNEY FAILURE, and RAPIDLY PROGRESSIVE COURSE.
DIAGNOSIS IS MADE BY BIOPSY (relevant protocol); BIOPSY IS NOT PERFORMED IN EVERYONE but IS REQUIRED if there is PROTEINURIA, DECREASE IN KIDNEY FUNCTION, or RAPID DETERIORATION.
MOST COMMON ERROR — THE "BENIGN" LABEL: in a young patient with isolated microscopic hematuria, normal kidney function, and no proteinuria, the course IS USUALLY GOOD, but A PORTION PROGRESSES OVER DECADES → FOLLOW-UP IS NOT TERMINATED, PROTEINURIA, BLOOD PRESSURE, and KIDNEY FUNCTION are reassessed at PLANNED INTERVALS; NEWLY DEVELOPED PROTEINURIA or RISING BLOOD PRESSURE CHANGES THE EVALUATION.
PROTEINURIA IS THE STRONGEST AND MOST MODIFYABLE PREDICTOR OF OUTCOME and IS THE TARGET OF TREATMENT.
SUPPORTIVE TREATMENT IS MAXIMIZED BEFORE STARTING IMMUNOSUPPRESSIVE THERAPY:
RENIN-ANGIOTENSIN BLOCKADE IS TITRATED TO THE HIGHEST TOLERATED DOSE, BLOOD PRESSURE IS TARGETED, SALT IS RESTRICTED, WEIGHT IS MANAGED, SMOKING IS STOPPED, and NEPHROTOXIC EXPOSURES ARE ELIMINATED (relevant protocol); THIS PERIOD SHOULD BE MAINTAINED FOR AN ADEQUATE TIME AND RESPONSE SHOULD BE EVALUATED.
IMMUNOSUPPRESSIVE THERAPY IS CONSIDERED IN PATIENTS SELECTED FOR IT and CARRIES SERIOUS RISK OF SIDE EFFECTS; DECISION IS MADE BY THE SPECIALIST.
SECONDARY CAUSES SHOULD BE EXCLUDED:
LIVER CIRRHOSIS (relevant protocol), INFLAMMATORY BOWEL DISEASES, CELIAC DISEASE, and CERTAIN SKIN DISEASES.
IF CREATININE RISES DURING A VISIBLE HEMATURIA ATTACK, THIS IS USUALLY TEMPORARY but SHOULD BE MONITORED AND CASES THAT DO NOT IMPROVE SHOULD BE RE-EVALUATED.
ALL DOSES SHOULD BE VERIFIED FROM THE INSTITUTIONAL PROTOCOL.

Drug	Adult	Pediatric	Route	Duration
TIMING IS DISTINGUISHING — simultaneous bleeding The simultaneity of the bleeding with the infection is one of the rare clues in the history that differentiates the two diseases. In both diseases, the patient experiences an upper respiratory tract infection and then sees blood in the urine; because of this similarity, the two pictures are often confused. However, the underlying processes are different, and this difference is reflected in the timing. In the post-streptococcal picture, it takes time for the body’s immune response to develop and create deposits in the kidney; therefore, hematuria appears weeks after the infection has completely resolved. In IgA nephropathy, on the other hand, pre-existing abnormal molecules rapidly increase together with the infection, and bleeding begins on the same days as the infection itself. For this reason, the patient should be asked whether the sore throat is still present.	CLASSIC PICTURE: VISIBLE HEMATURIA EMERGING ON THE SAME DAYS AS UPPER RESPIRATORY TRACT INFECTION. THE PATIENT TYPICALLY SAYS, 'MY URINE DARKENED WHILE MY THROAT HURT.' IN POST-STREPTOCOCCAL GLOMERULONEPHRITIS, HOWEVER, THE HEMATURIA APPEARS WEEKS AFTER THE INFECTION (according to the relevant protocol). THIS DISTINCTION CAN BE MADE WITH A SINGLE QUESTION IN THE HISTORY: 'WHEN THE COLOR OF YOUR URINE CHANGED, WAS YOUR THROAT STILL HURTING OR HAD WEEKS PASSED?' THE BLEEDING LASTS A FEW DAYS, RESOLVES SPONTANEOUSLY, AND MAY RECUR	This picture is common in children and adolescents	—	At the first assessment
THE 'BENIGN' LABEL — hides the thirty-year course The fact that the label 'benign' hides a thirty-year course is the most important point in determining the follow-up decision in this disease. In a young patient, microscopic bleeding is accidentally found, examinations are performed, kidney function and proteinuria are normal, and the patient is told there is nothing to worry about and follow-up is closed. This approach is correct in the short term; indeed, most patients do not develop any problems. However, the timeframe of this disease is measured not in years but in decades. The silent process that begins in a twenty-five-year-old patient can manifest as end-stage renal failure at fifty, and the patient may not report any complaints in the intervening twenty-five years. This period is also an opportunity; with regular follow-up, proteinuria can be detected as soon as it appears, and treatment can be started.	In a young patient with ISOLATED MICROSCOPIC HEMATURIA, NORMAL KIDNEY FUNCTION, and NO PROTEINURIA, the course is MOSTLY GOOD; however, A PORTION PROGRESSES TO END-STAGE RENAL DISEASE OVER DECADES. A PATIENT DIAGNOSED AT TWENTY-FIVE MAY GO ON DIALYSIS BY FIFTY. FOR THIS REASON, FOLLOW-UP IS NOT CLOSED: URINE PROTEIN, BLOOD PRESSURE, and KIDNEY FUNCTION are reassessed at PLANNED INTERVALS. NEWLY EMERGING PROTEINURIA, RISING BLOOD PRESSURE, and DECREASING KIDNEY FUNCTION CHANGE THE EVALUATION AND REQUIRE NEPHROLOGY REFERRAL	Long-term follow-up should also be planned in children.	—	For life
PROTEINURIA — Both a predictor of course and a treatment target The fact that proteinuria is both a predictor of course and a treatment target clarifies what follow-up should focus on in this disease. Many findings in kidney diseases indicate how advanced the disease is but do not provide a target to work on; creatinine is one of them – it signals that damage has occurred when elevated but cannot be directly lowered. Proteinuria is different; it both predicts how quickly the disease will progress and can be reduced with treatment, and when reduced, progression slows. Possessing these two features together places it at the center of follow-up. Therefore, it should be measured at every check-up, the trend over time rather than a single value should be evaluated, and treatment decisions should be made according to this trend.	PROTEINURIA IS THE STRONGEST AND MOST MODIFIABLE COURSE DETERMINANT IN THIS DISEASE: THE HIGHER THE LEVEL, THE FASTER THE PROGRESSION, AND WHEN REDUCED, PROGRESSION SLOWS. THEREFORE, PROTEINURIA IS NOT JUST A MONITORED VALUE BUT A DIRECT TARGET OF TREATMENT. OTHER POOR PROGNOSIS INDICATORS: REDUCED KIDNEY FUNCTION AT DIAGNOSIS, HIGH BLOOD PRESSURE, FIBROSIS DOMINANCE IN BIOPSY, OBESITY, AND SMOKING. Target values should be confirmed from the INSTITUTIONAL PROTOCOL.	In children, targets are determined according to age.	—	Throughout follow-up
SUPPORTIVE TREATMENT FIRST AND AT THE HIGHEST LEVEL Not switching to immunosuppressive therapy before maximizing supportive therapy protects against unnecessary and severe side effects. When a patient with high proteinuria is seen, there is a desire to start strong treatment; the disease seems progressive, and waiting feels like a waste of time. However, in a significant portion of patients, proteinuria decreases markedly with only blood pressure control and appropriately dosed blockade therapy, and in these patients, immunosuppressive therapy is not needed at all. These therapies, on the other hand, have serious side effects; severe infection, high blood sugar, and bone loss are among the main ones. Therefore, supportive therapy should be maintained for a sufficient period and at the highest tolerated dose, and the decision should be made at the end of this period.	BEFORE SWITCHING TO IMMUNOSUPPRESSIVE THERAPY, SUPPORTIVE THERAPY SHOULD BE MAXIMIZED and MAINTAINED FOR A SUFFICIENT PERIOD: RENIN-ANGIOTENSIN BLOCKADE SHOULD BE RAISED TO THE HIGHEST TOLERATED DOSE (checking creatinine and potassium), BLOOD PRESSURE SHOULD BE BROUGHT TO TARGET, SALT SHOULD BE RESTRICTED, WEIGHT MANAGED, SMOKING STOPPED, and NEPHROTOXIC EXPOSURE HALTED (relevant protocol). AT THE END OF THIS PERIOD, PROTEINURIA SHOULD BE RE-EVALUATED; A SIGNIFICANT PORTION OF PATIENTS ACHIEVE TARGETS WITH ONLY THIS THERAPY. TWO DIFFERENT BLOCKERS SHOULD NOT BE USED TOGETHER (relevant protocol)	Drug selection and doses in children are determined by specialist decision	—	Continuous
SECONDARY CAUSES SHOULD BE INVESTIGATED Searching for secondary causes prevents the disease from being considered merely a kidney-limited problem. The abnormal molecule that accumulates in the kidney is the result of a production and clearance balance closely related to the intestines and liver; when this balance is disturbed, accumulation increases. In liver cirrhosis, the clearance capacity decreases and the molecule remains in circulation. In inflammatory bowel diseases and celiac disease, immune stimulation on the intestinal surface increases production. Some of these diseases may be undiagnosed, and the kidney finding may appear as the first sign. Additionally, the same process has a systemic form that manifests in the skin, joints, and intestines; therefore, rash, abdominal pain, and joint complaints should be questioned.	SECONDARY CAUSES TO BE INVESTIGATED: LIVER CIRRHOSIS and PORTAL HYPERTENSION (relevant protocol), INFLAMMATORY BOWEL DISEASES, CELIAC DISEASE, CERTAIN SKIN DISEASES, CHRONIC INFECTIONS, and SOME RHEUMATIC DISEASES. In addition, it should be kept in mind that IgA VASCULITIS can have a SYSTEMIC FORM WITH THE SAME PROCESS, and SKIN RASH, ABDOMINAL PAIN, and JOINT COMPLAINTS should be asked about (relevant protocol). IF A SECONDARY CAUSE IS FOUND, TREATMENT SHOULD ALSO BE DIRECTED AT THAT DISEASE	In children, coexistence with IgA vasculitis is more frequent	—	At the diagnostic stage
Increase in creatinine during a bleeding attack The fact that creatinine elevation during a bleeding attack is usually temporary prevents unnecessary interventions while necessitating monitoring. During visible bleeding, many blood cells pass into the urine; these cells accumulate in the small renal tubules, creating a temporary blockage and disturbing the flow of filtered fluid. As a result, creatinine rises, and the condition appears similar to acute kidney injury. When the attack passes, the tubules are cleared, and values usually return to their previous levels. This information prevents unnecessary alarm and interventions. However, not every elevation can be explained for this reason; a transition to the rapidly progressive form of the disease can give the same picture. Therefore, creatinine should be re-measured after the attack, and if it does not improve, further evaluation should be performed.	CREATININE CAN RISE DURING VISIBLE BLEEDING ATTACKS; THIS CONDITION IS USUALLY TEMPORARY and is due to the blockage of the urinary tract with blood cells. HOWEVER, IT SHOULD BE MONITORED, and creatinine should be re-measured after the attack; in cases where it does not improve or rises significantly, a rapidly progressive condition should be considered and REPEAT BIOPSY should be discussed (relevant protocols). DURING THE ATTACK, NEPHROTOXIC DRUGS SHOULD BE AVOIDED and ADEQUATE FLUID INTAKE should be ensured.	In children, post-attack control should also be performed.	—	During and after the attack
Immunosuppressive therapy and referral The reason immunosuppressive treatment is not given to everyone is due to the narrow balance of benefit versus harm in this disease. The name of the disease indicates an inflammatory process, and suppressing the inflammation seems reasonable. However, in these patients, the benefit of the treatment is limited and has only been shown in a specific risk group; on the other hand, side effects are significant and can leave long-term consequences in a young patient. Severe infections are the most dangerous of these. Therefore, the decision should be made after supportive treatment has been applied for a sufficient period and the risk of progression has been evaluated. The decision belongs to the specialist because both biopsy findings and the patient’s risk profile must be evaluated together.	IMMUNOSUPPRESSIVE TREATMENT IS NOT GIVEN TO EVERYONE; it comes into consideration in SELECTED patients whose proteinuria remains high despite supportive treatment and who are at risk of progression, and the DECISION BELONGS TO THE SPECIALIST. THESE TREATMENTS CARRY SERIOUS SIDE EFFECT RISKS: SEVERE INFECTION, HIGH BLOOD SUGAR, BONE LOSS, and STOMACH PROBLEMS. INFECTION SCREENING and PREVENTIVE MEASURES should be planned before treatment (relevant protocols). REFERRAL INDICATIONS: RAPIDLY DECREASING KIDNEY FUNCTION, RESISTANT PROTEINURIA, NEPHROTIC SYNDROME, RESISTANT HIGH BLOOD PRESSURE, and DIAGNOSTIC SUSPICION	The decision for the child is made in the specialist center	—	In selected patients

Alternative

Post-streptococcal glomerulonephritis, hematuria occurs weeks after the infection (relevant protocol).
Thin basement membrane disease causes familial microscopic hematuria and has a good course.
Alport syndrome should be considered with hearing loss and family history.
Hematuria originating from the urinary tract is distinguished by clot and proteinuria-free presentation (relevant protocol).
IgA vasculitis is the systemic form of the same process (relevant protocol).
Lupus nephritis is distinguished by systemic findings and laboratory tests (relevant protocol).
ANCA-associated vasculitis should be considered in rapidly progressive cases (relevant protocol).
Membranous nephropathy and other nephrotic syndromes are distinguished by biopsy (relevant protocol).
Diabetic kidney disease, if present, complicates the presentation (relevant protocol).
Exercise-induced transient hematuria is excluded by repeated testing (relevant protocol).

Red flags

NOT ASKING ABOUT THE TIMING, → in both diseases, the patient HAS AN UPPER RESPIRATORY TRACT INFECTION AND THEN SEES BLOOD IN HIS URINE; BECAUSE OF THIS SIMILARITY, THE TWO TABLES ARE OFTEN CONFUSED. IT TAKES TIME for the immune response to occur after STREPTOCOCCUS and the bleeding occurs WEEKS AFTER THE INFECTION HAS COMPLETELY PASSED; In IgA NEPHROPATHY, BLEEDING BEGINS ON THE SAME DAYS AS THE INFECTION ITSELF.
THIS APPROACH IS CORRECT IN THE SHORT TERM → CLOSING THE FOLLOW-UP BY CALLING A YOUNG PATIENT WITH ISOLATED MICROSCOPIC BLEEDING "BENIGN", BUT THE TIMESCALE OF THIS DISEASE IS MEASURED IN DECADES, NOT YEARS: THE SILENT PROCESS THAT BEGINS AT THE AGE OF TWENTY-FIVE MAY MANIFEST AS END-STAGE RENAL FAILURE AT THE AGE OF FIFTY, AND THE PATIENT DOES NOT DESCRIBE ANY COMPLAINTS FOR THE TWENTY-FIVE YEARS IN BETWEEN.
PROTEIN CAN BE DETECTED AS SOON AS PROTEIN OCCURS → REGULAR FOLLOW-UP AND TREATMENT CAN BE STARTED NOT TO RE-EVALUATE BLOOD PRESSURE and KIDNEY FUNCTION.
THE FACT THAT PROTEIN IS CONSIDERED ONLY A MONITORED VALUE → BOTH PREDICTS HOW FAST THE DISEASE WILL PROGRESS AND CAN BE REDUCED WITH TREATMENT, AND WHEN IT DECREASES, PROGRESSION SLOWS DOWN; The fact that it carries these two features together places it at the CENTER OF THE MONITORING.
TO MAKE A DECISION BASED ON A SINGLE PROTEIN VALUE → TREND OVER TIME should be evaluated.
PROTEINURIA IS SIGNIFICANTLY REDUCED IN A SIGNIFICANT PROPORTION OF PATIENTS → SWITCHING TO IMMUNOSUPPRESSIVE THERAPY WITHOUT MAXIMIZING SUPPORTIVE THERAPY, AND IMMUNOSUPPRESSIVE THERAPY IS NOT REQUIRED AT ALL IN THESE PATIENTS; however, these treatments have serious side effects such as SEVERE INFECTION, SUGAR INCREASE and BONE LOSS.
FAILURE TO INCREASE RENIN-ANGIOTENSIN BLOCKADE TO THE HIGHEST TOLERATED DOSE and failure to control potassium with creatinine.
CONCOMITANT USE OF TWO DIFFERENT BLOCKERS (corresponding protocol).
The molecule that accumulates in the kidney → not looking for secondary causes is the result of a balance closely related to the INTESTINE and the LIVER: IN CIRRHOSIS, THE CLEARANCE CAPACITY DECREASES, IN INFLAMMATORY BOWEL DISEASE and in CELIAC, IMMUNE STIMULATION ON THE INTESTINAL SURFACE INCREASES PRODUCTION. Some of these diseases may not be DIAGNOSED and KIDNEY FINDING MAY BE THE FIRST SIGN.
THERE IS A SYSTEMIC FORM OF THE SAME PROCESS → NOT QUESTIONING SKIN RASH, ABDOMINAL PAIN and JOINT COMPLAINTS.
The increase in CREATININE during a BLEEDING ATTACK should not always be considered temporary → blood cells passing into the URINE during the attack accumulate in SMALL TUBULES, causing a TEMPORARY OBSTRUCTION, and the values generally RETURN; however, NOT EVERY INCREASE CAN BE EXPLAINED BY THIS — RAPID PROGRESSION also presents the same picture → CREATININE SHOULD BE RE-MEASURED AFTER THE ATTACK.
Administration of NEPHROTOXIC DRUGS during the attack.
Skipping INFECTION SCREENING and PROTECTIVE MEASURES before IMMUNOSUPPRESSIVE THERAPY.

Disposition and follow-up

Green zone: Patient with isolated microscopic hematuria, no proteinuria, normal kidney function, and blood pressure: assessment of proteinuria, blood pressure, and kidney function at planned intervals before closing follow-up.
Yellow zone: Patient with newly emerging or increasing proteinuria, rising blood pressure, declining kidney function, nephrotic-level protein loss, suspicion of a secondary cause, or requiring biopsy: referral to nephrology and further evaluation.
Red zone: Active urinary sediment with rapidly declining kidney function: urgent assessment for rapidly progressing glomerulonephritis (relevant protocol). Significant decrease in urine output and fluid overload: urgent assessment (relevant protocol). Headache, visual disturbance, or neurological findings with high blood pressure: urgent evaluation for hypertensive emergency (relevant protocol). Combination of fever, rash, and abdominal pain: urgent assessment for systemic involvement (relevant protocol). Fever under immunosuppressive therapy: urgent assessment (relevant protocol).

Key clinical points

READ FIRST — timing and the 'benign' trap

TIMING DISTINGUISHES TWO DISEASES — one of the rare differentiations in the story made with a SINGLE QUESTION | In both diseases, the patient experiences AN UPPER RESPIRATORY TRACT INFECTION and THEN SEES BLOOD IN THE URINE → because of this similarity, THE TWO CONDITIONS ARE OFTEN CONFUSED | HOWEVER, THE UNDERLYING PROCESSES ARE DIFFERENT and THIS DIFFERENCE REFLECTS IN TIMING | POST-STREPTOCOCCAL: it takes TIME for the body's IMMUNE RESPONSE TO DEVELOP and for DEPOSITS TO FORM IN THE KIDNEY → urinary bleeding appears WEEKS AFTER THE INFECTION HAS COMPLETELY RESOLVED | IgA NEPHROPATHY: the ABNORMAL MOLECULE PRESENT IN ADVANCE INCREASES RAPIDLY WITH THE INFECTION → bleeding begins ON THE SAME DAYS AS THE INFECTION | QUESTION: 'WHEN THE COLOR OF YOUR URINE CHANGED, WAS YOUR SORE THROAT STILL PRESENT OR HAD WEEKS PASSED?' | Patients usually say 'MY URINE DARKENED WHILE MY THROAT WAS SORE' | Bleeding LASTS A FEW DAYS, SUBSIDES SPONTANEOUSLY, and CAN RECUR | THE 'BENIGN' LABEL HIDES THE THIRTY-YEAR COURSE — the MOST IMPORTANT point guiding follow-up decisions | A young patient is FOUND TO HAVE MICROSCOPIC BLEEDING BY CHANCE → tests are performed → KIDNEY FUNCTION and PROTEINURIA ARE NORMAL → the patient is told THERE IS NOTHING TO WORRY ABOUT and FOLLOW-UP IS CLOSED | THIS APPROACH IS CORRECT IN THE SHORT TERM: in most patients, THERE REALLY IS NO PROBLEM | HOWEVER, THE TIME SCALE OF THIS DISEASE IS MEASURED NOT IN YEARS BUT IN DECADES | A SILENT PROCESS STARTING AT TWENTY-FIVE CAN EMERGE AT FIFTY AS END-STAGE RENAL FAILURE, and DURING THE INTERVENING TWENTY-FIVE YEARS THE PATIENT REPORTS NO SYMPTOMS | THIS PERIOD IS ALSO AN OPPORTUNITY: with regular follow-up, PROTEINURIA CAN BE DETECTED AS SOON AS IT APPEARS and TREATMENT CAN BEGIN → FOLLOW-UP IS NOT CLOSED

Timing distinguishes two diseases: in post-streptococcal cases, bleeding appears weeks after the infection because the immune response takes time, whereas in IgA nephropathy, the pre-existing abnormal molecule increases with the infection and bleeding starts on the same days. The benign label hides the thirty-year course: in a young patient, when tests are normal follow-up is closed, which is correct in the short term, but the time scale of this disease is measured in decades, and a silent process starting at twenty-five can appear as end-stage failure at fifty. This period is also an opportunity because proteinuria can be detected as soon as it appears.

Why proteinuria is central; why supportive treatment comes first

PROTEINURIA IS BOTH A PROGNOSTIC INDICATOR AND A TREATMENT TARGET — it clarifies what the follow-up should focus on | IN MANY FINDINGS IN KIDNEY DISEASES indicate HOW ADVANCED THE DISEASE IS, but DO NOT PROVIDE A TARGET TO WORK ON: CREATININE is one of them — when elevated, it signals DAMAGE HAS OCCURRED but CANNOT BE DIRECTLY REDUCED | PROTEINURIA IS DIFFERENT: (1) it PREVIOUSLY INDICATES HOW RAPIDLY THE DISEASE WILL PROGRESS | (2) IT CAN BE REDUCED WITH TREATMENT and when reduced, progression slows | CARRYING THESE TWO CHARACTERISTICS TOGETHER places it at the CENTER OF MONITORING → it is measured at every check-up, and the TREND OVER TIME is evaluated instead of a SINGLE VALUE | OTHER POOR PROGNOSTIC INDICATORS: DECREASED KIDNEY FUNCTION AT DIAGNOSIS | HIGH BLOOD PRESSURE | PREDOMINANCE OF SCAR TISSUE IN BIOPSY | OBESITY | SMOKING | SUPPORTIVE THERAPY FIRST AND AT THE HIGHEST LEVEL — protects from unnecessary and SEVERE SIDE EFFECTS | When a patient with high proteinuria is seen, a STRONG DESIRE TO START TREATMENT arises: the disease appears PROGRESSIVE and WAITING SEEMS LIKE A LOSS OF TIME | HOWEVER, in a SIGNIFICANT PORTION of patients, proteinuria DECREASES SIGNIFICANTLY WITH ONLY BLOOD PRESSURE CONTROL and APPROPRIATE DOSE BLOCKADE → IN THESE PATIENTS, IMMUNOSUPPRESSIVE THERAPY IS NOT NEEDED AT ALL | THESE THERAPIES HAVE SERIOUS SIDE EFFECTS: SEVERE INFECTION | INCREASED BLOOD SUGAR | BONE LOSS | RULE: supportive therapy is MAINTAINED FOR SUFFICIENT DURATION AND AT THE HIGHEST TOLERATED DOSE, DECISION IS MADE AT THE END OF THIS PERIOD | SUPPORTIVE PACKAGE: RENIN-ANGIOTENSIN BLOCKADE TO HIGHEST TOLERATED DOSE (monitoring creatinine + potassium) | BLOOD PRESSURE TARGETING | SALT RESTRICTION | WEIGHT MANAGEMENT | SMOKING CESSATION | AVOIDANCE OF NEPHROTOXIC EXPOSURE | TWO DIFFERENT BLOCKERS ARE NOT USED TOGETHER

Proteinuria is both a prognostic indicator and a treatment target: creatinine elevation signals damage has occurred but cannot be directly reduced, whereas proteinuria both indicates the rate of progression and can be reduced with treatment; when reduced, progression slows. Therefore, the trend over time should be monitored. Immunosuppressive therapy should not be started before supportive treatment is maximized because in a significant portion of patients, proteinuria decreases significantly with only blood pressure control and appropriate dose blockade, and these patients do not require treatment that carries a risk of severe infection.

Secondary causes, creatinine during attack, and treatment decision

SECONDARY CAUSES ARE SOUGHT — prevents the disease from being considered ONLY A KIDNEY-RESTRICTED PROBLEM | The ABNORMAL MOLECULE accumulated in the kidney is the result of a PRODUCTION and CLEARANCE BALANCE closely RELATED to THE INTESTINE and LIVER → when this balance is disrupted, ACCUMULATION INCREASES | IN LIVER CIRRHOSIS: CLEARANCE CAPACITY DECREASES and THE MOLECULE REMAINS IN CIRCULATION | IN INFLAMMATORY BOWEL DISEASES and CELIAC DISEASE: IMMUNE STIMULATION ON THE INTESTINAL SURFACE INCREASES PRODUCTION | SOME OF THESE DISEASES may NOT HAVE BEEN DIAGNOSED and KIDNEY FINDINGS may appear as the FIRST SIGN | TO BE INVESTIGATED: CIRRHOSIS and PORTAL HYPERTENSION | INFLAMMATORY BOWEL DISEASES | CELIAC | SOME SKIN DISEASES | CHRONIC INFECTIONS | SOME RHEUMATIC DISEASES | ADDITIONALLY: THERE IS A SYSTEMIC FORM OF THE SAME PROCESS THAT MANIFESTS IN SKIN, JOINTS, and INTESTINE → RASH, ABDOMINAL PAIN, and JOINT COMPLAINTS are questioned | IN BLEEDING ATTACKS, RISE IN CREATININE — prevents unnecessary intervention but MAKES FOLLOW-UP MANDATORY | During visible bleeding, MANY BLOOD CELLS PASS INTO THE URINE → these cells ACCUMULATE IN THE KIDNEY'S SMALL TUBULES, creating a TEMPORARY OBSTRUCTION, and DISRUPT THE FLOW OF FILTERED FLUID → CREATININE RISES and the picture APPEARS LIKE ACUTE KIDNEY INJURY | When the attack passes, TUBULES CLEAN and VALUES USUALLY RETURN TO ORIGINAL LEVEL → THIS INFORMATION PREVENTS UNNECESSARY PANIC and INTERVENTION | HOWEVER, NOT EVERY RISE CAN BE EXPLAINED BY THIS REASON: PROGRESSION TO THE RAPIDLY ADVANCING FORM OF THE DISEASE ALSO PRODUCES THE SAME PICTURE → AFTER THE ATTACK, CREATININE IS RECHECKED and IF IT DOES NOT IMPROVE, FURTHER EVALUATION is conducted | During the attack, NEPHROTOXIC DRUGS ARE AVOIDED and ADEQUATE FLUID is provided | IMMUNOSUPPRESSIVE THERAPY IS NOT GIVEN TO EVERYONE — the balance between benefit and harm is NARROW | The disease name INDICATES AN INFLAMMATORY PROCESS and SUPPRESSING INFLAMMATION SEEMS LOGICAL | HOWEVER, in these patients, the BENEFIT of therapy is LIMITED and has BEEN DEMONSTRATED ONLY IN A SPECIFIC RISK GROUP; on the other hand, SIDE EFFECTS ARE SIGNIFICANT and may leave LONG-TERM CONSEQUENCES in a YOUNG PATIENT — SEVERE INFECTIONS ARE THE MOST DANGEROUS | RULE: the decision is given AFTER SUPPORTIVE THERAPY IS APPLIED FOR SUFFICIENT TIME and PROGRESSION RISK IS EVALUATED; THE DECISION BELONGS TO THE SPECIALIST because BOTH BIOPSY FINDINGS AND THE PATIENT'S RISK PROFILE are evaluated together | INFECTION SCREENING and PREVENTIVE MEASURES are planned BEFORE TREATMENT

Secondary causes should be investigated because the accumulated molecule is the result of a balance related to the intestine and liver; in cirrhosis, clearance decreases, in inflammatory bowel disease and celiac disease production increases, and these diseases may be undiagnosed. The rise in creatinine during a bleeding attack is usually temporary because blood cells passing into the urine create temporary blockages in the tubules, but not every rise can be explained by this and it should be re-measured after the attack. Immunosuppressive therapy is not given to everyone because the benefit is limited and specific to a certain risk group, whereas side effects can leave long-term consequences in young patients.

Featured external sources

KDIGO 2025 IgA nephropathy and IgA vasculitis guideline.Current evidence and guideline summary.
KDIGO 2025 IgAN/IgAV full guideline PDF.Full guideline text.
KDIGO Glomerular Diseases.Official guideline hub.

Detailed assessment

Diagnostic and decision reasoning

Clinical framework

Overview

IgA nephropathy is the most common primary glomerular disease worldwide and its classic presentation directly gives the diagnosis: visible hematuria occurring on the same days as an upper respiratory tract infection. The timing is distinctive because in post-streptococcal glomerulonephritis, hematuria occurs weeks after the infection.

The spectrum of disease presentation is very broad. The most common mistake is to declare a young patient with isolated microscopic hematuria as benign and stop follow-up; a portion of these patients progress to end-stage renal failure over decades.

The basis of treatment is supportive therapy that reduces proteinuria, and immunosuppressive therapy is not started without maximizing this treatment.

Differential diagnosis and assessment

Key considerations

Post-streptococcal glomerulonephritis, hematuria occurs weeks later (refer to relevant protocol).
Thin basement membrane disease causes familial microscopic hematuria.
Alport syndrome is considered with hearing loss and family history.
Urinary tract-origin hematuria is distinguished with a non-proteinuric presentation (refer to relevant protocol).
IgA vasculitis is the systemic form of the same process (relevant protocol).
Lupus nephritis is differentiated with systemic findings (relevant protocol).
ANCA-associated vasculitis is considered in rapidly progressive cases (refer to relevant protocol).
Other nephrotic presentations are distinguished by biopsy (refer to relevant protocol).
Diabetic kidney disease, if present, can confound (refer to relevant protocol).
Exercise-induced transient hematuria is excluded by repeated testing (relevant protocol).

Clinical decision reasoning

Why it matters

The points that determine the clinical outcome in this disease are related to how the diagnosis is made and how long the follow-up lasts. The first point is that timing is distinctive; a single question differentiates the two diseases.

The second and most harmful point is closing the follow-up with a benign label; the time scale of the disease is measured in decades. The third point is that proteinuria is both a determinant of progression and a treatment target.

The fourth point is maximizing supportive treatment; a significant portion of patients reaches the target at this stage. The fifth point is searching for secondary causes.

The sixth point is that creatinine elevation during attacks is usually temporary. The final point is that immunosuppressive treatment has a narrow benefit-risk balance.

Safety and monitoring

Complications and safety

Critical complications

It can progress to end-stage renal failure over decades (relevant protocol).
It can progress to a rapidly progressive form of glomerulonephritis (relevant protocol).
Nephrotic-level protein loss can develop (relevant protocol).
Resistant high blood pressure may appear.
Temporary acute kidney injury is observed during bleeding attacks.
Severe infection may develop due to immunosuppressive therapy.
Blood sugar elevation and bone loss may be seen due to treatment.
Blood pressure and proteinuria may worsen during pregnancy (relevant protocol).
Recurrence in the graft can be seen after transplantation (relevant protocol).

Special patient populations

Special considerations

The condition is common in children and adolescents, and long-term follow-up should be planned.
Blood pressure and proteinuria monitoring in pregnant women should be increased, and medications should be adjusted in advance (relevant protocol).
Secondary form should be considered in patients with liver cirrhosis (relevant protocol).
The relationship should be observed in patients with inflammatory bowel disease and celiac disease.
Recurrence in the graft should be monitored in the transplant recipient (relevant protocol).
Infection protection should be planned in patients receiving immunosuppressive treatment (relevant protocol).
Treatment targets change in advanced-stage renal failure (relevant protocol).
Progression is faster in obese and smoking patients.

Follow-up and reassessment

Follow-up plan

IgA nephropathy monitoring should continue lifelong and should not be discontinued even in patients with isolated microscopic hematuria. Protein-to-creatinine ratio in urine, blood pressure, and kidney function should be evaluated at planned intervals; proteinuria should be interpreted not as a single value but as a trend over time.

In patients on supportive treatment, it should be reviewed whether blockade therapy has been increased to the highest tolerated dose and whether creatinine and potassium have been monitored. Salt restriction, weight management, and smoking cessation should be addressed at every visit.

After visible hematuria attacks, creatinine should be remeasured, and if it does not normalize, further evaluation should be performed. Secondary causes and signs of systemic involvement should be investigated.

In patients receiving immunosuppressive therapy, infection monitoring, blood sugar, and bone health should be planned. Patients should be informed about warning signs; an increase in foamy urine, swelling in the feet, reduced urine output, high blood pressure, fever, and newly occurring rash with abdominal pain require immediate consultation.